Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
A family of inhibitory proteins which bind to the REL PROTO-ONCOGENE PROTEINS and modulate their activity. In the CYTOPLASM, I-kappa B proteins bind to the transcription factor NF-KAPPA B. Cell stimulation causes its dissociation and translocation of active NF-kappa B to the nucleus.
Carbamates in which the -CO- group has been replaced by a -CS- group.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A class of opioid receptors recognized by its pharmacological profile. Kappa opioid receptors bind dynorphins with a higher affinity than endorphins which are themselves preferred to enkephalins.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Cellular DNA-binding proteins encoded by the rel gene (GENES, REL). They are expressed predominately in hematopoietic cells and may play a role in lymphocyte differentiation. Rel frequently combines with other related proteins (NF-KAPPA B, I-kappa B, relA) to form heterodimers that regulate transcription. Rearrangement or overexpression of c-rel can cause tumorigenesis.
A component of NF-kappa B transcription factor. It is proteolytically processed from NF-kappa B p105 precursor protein and is capable of forming dimeric complexes with itself or with TRANSCRIPTION FACTOR RELA. It regulates expression of GENES involved in immune and inflammatory responses.
A subunit of NF-kappa B that is primarily responsible for its transactivation function. It contains a C-terminal transactivation domain and an N-terminal domain with homology to PROTO-ONCOGENE PROTEINS C-REL.
A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
One of the types of light chains of the immunoglobulins with a molecular weight of approximately 22 kDa.
Established cell cultures that have the potential to propagate indefinitely.
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A transcription factor that takes part in the NF-kappa-B complex by interacting with NF-KAPPA B P50 SUBUNIT or NF-KAPPA B P52 SUBUNIT. It regulates GENETIC TRANSCRIPTION that is involved in immune and inflammatory responses.
An enzyme that catalyzes the acetylation of chloramphenicol to yield chloramphenicol 3-acetate. Since chloramphenicol 3-acetate does not bind to bacterial ribosomes and is not an inhibitor of peptidyltransferase, the enzyme is responsible for the naturally occurring chloramphenicol resistance in bacteria. The enzyme, for which variants are known, is found in both gram-negative and gram-positive bacteria. EC 2.3.1.28.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Cis-acting DNA sequences which can increase transcription of genes. Enhancers can usually function in either orientation and at various distances from a promoter.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.
Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Regulatory sequences important for viral replication that are located on each end of the HIV genome. The LTR includes the HIV ENHANCER, promoter, and other sequences. Specific regions in the LTR include the negative regulatory element (NRE), NF-kappa B binding sites , Sp1 binding sites, TATA BOX, and trans-acting responsive element (TAR). The binding of both cellular and viral proteins to these regions regulates HIV transcription.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Tumor suppressor genes located on the long arm of human chromosome 17 in the region 17q11.2. Mutation of these genes is thought to cause NEUROFIBROMATOSIS 1, Watson syndrome, and LEOPARD syndrome.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A protein found most abundantly in the nervous system. Defects or deficiencies in this protein are associated with NEUROFIBROMATOSIS 1, Watson syndrome, and LEOPARD syndrome. Mutations in the gene (GENE, NEUROFIBROMATOSIS 1) affect two known functions: regulation of ras-GTPase and tumor suppression.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
An autosomal dominant inherited disorder (with a high frequency of spontaneous mutations) that features developmental changes in the nervous system, muscles, bones, and skin, most notably in tissue derived from the embryonic NEURAL CREST. Multiple hyperpigmented skin lesions and subcutaneous tumors are the hallmark of this disease. Peripheral and central nervous system neoplasms occur frequently, especially OPTIC NERVE GLIOMA and NEUROFIBROSARCOMA. NF1 is caused by mutations which inactivate the NF1 gene (GENES, NEUROFIBROMATOSIS 1) on chromosome 17q. The incidence of learning disabilities is also elevated in this condition. (From Adams et al., Principles of Neurology, 6th ed, pp1014-18) There is overlap of clinical features with NOONAN SYNDROME in a syndrome called neurofibromatosis-Noonan syndrome. Both the PTPN11 and NF1 gene products are involved in the SIGNAL TRANSDUCTION pathway of Ras (RAS PROTEINS).
A neoplasm originating from thymic tissue, usually benign, and frequently encapsulated. Although it is occasionally invasive, metastases are extremely rare. It consists of any type of thymic epithelial cell as well as lymphocytes that are usually abundant. Malignant lymphomas that involve the thymus, e.g., lymphosarcoma, Hodgkin's disease (previously termed granulomatous thymoma), should not be regarded as thymoma. (From Stedman, 25th ed)
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
A GLUTATHIONE dimer formed by a disulfide bond between the cysteine sulfhydryl side chains during the course of being oxidized.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
A specific protein kinase C inhibitor, which inhibits superoxide release from human neutrophils (PMN) stimulated with phorbol myristate acetate or synthetic diacylglycerol.
A multiprotein complex composed of the products of c-jun and c-fos proto-oncogenes. These proteins must dimerize in order to bind to the AP-1 recognition site, also known as the TPA-responsive element (TRE). AP-1 controls both basal and inducible transcription of several genes.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Enzymes that oxidize certain LUMINESCENT AGENTS to emit light (PHYSICAL LUMINESCENCE). The luciferases from different organisms have evolved differently so have different structures and substrates.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Nucleic acid sequences involved in regulating the expression of genes.
A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known CONSERVED SEQUENCE set is represented by a consensus sequence. Commonly observed supersecondary protein structures (AMINO ACID MOTIFS) are often formed by conserved sequences.
Sequences of DNA or RNA that occur in multiple copies. There are several types: INTERSPERSED REPETITIVE SEQUENCES are copies of transposable elements (DNA TRANSPOSABLE ELEMENTS or RETROELEMENTS) dispersed throughout the genome. TERMINAL REPEAT SEQUENCES flank both ends of another sequence, for example, the long terminal repeats (LTRs) on RETROVIRUSES. Variations may be direct repeats, those occurring in the same direction, or inverted repeats, those opposite to each other in direction. TANDEM REPEAT SEQUENCES are copies which lie adjacent to each other, direct or inverted (INVERTED REPEAT SEQUENCES).
Synthetic or natural oligonucleotides used in hybridization studies in order to identify and study specific nucleic acid fragments, e.g., DNA segments near or within a specific gene locus or gene. The probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the probe include the radioisotope labels 32P and 125I and the chemical label biotin.
Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed)
The N-acetyl derivative of CYSTEINE. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
Transforming proteins coded by rel oncogenes. The v-rel protein competes with rel-related proteins and probably transforms cells by acting as a dominant negative version of c-rel. This results in the induction of a broad range of leukemias and lymphomas.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.
Genetic loci in the vertebrate major histocompatibility complex which encode polymorphic characteristics not related to immune responsiveness or complement activity, e.g., B loci (chicken), DLA (dog), GPLA (guinea pig), H-2 (mouse), RT-1 (rat), HLA-A, -B, and -C class I genes of man.
Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.
A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
An inhibitor of Serine Endopeptidases. Acts as alkylating agent and is known to interfere with the translation process.
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
The rate dynamics in chemical or physical systems.
Enzyme complexes that catalyze the formation of PROSTAGLANDINS from the appropriate unsaturated FATTY ACIDS, molecular OXYGEN, and a reduced acceptor.
Transport proteins that carry specific substances in the blood or across cell membranes.
An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)
Proteins prepared by recombinant DNA technology.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kDa. There are two major types of light chains, kappa and lambda. Two Ig light chains and two Ig heavy chains (IMMUNOGLOBULIN HEAVY CHAINS) make one immunoglobulin molecule.
An autosomal dominant disorder characterized by a high incidence of bilateral acoustic neuromas as well as schwannomas (NEURILEMMOMA) of other cranial and peripheral nerves, and other benign intracranial tumors including meningiomas, ependymomas, spinal neurofibromas, and gliomas. The disease has been linked to mutations of the NF2 gene (GENES, NEUROFIBROMATOSIS 2) on chromosome 22 (22q12) and usually presents clinically in the first or second decade of life.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Elements of limited time intervals, contributing to particular results or situations.
DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.
Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues.
Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.
Ordered rearrangement of B-lymphocyte variable gene regions coding for the kappa or lambda IMMUNOGLOBULIN LIGHT CHAINS, thereby contributing to antibody diversity. It occurs during the second stage of differentiation of the IMMATURE B-LYMPHOCYTES.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
A sulfhydryl reagent which oxidizes sulfhydryl groups to the disulfide form. It is a radiation-sensitizing agent of anoxic bacterial and mammalian cells.
A cell line derived from cultured tumor cells.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A protein subunit that takes part in forming nuclear factor 90 protein complexes.
Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.
A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).
One of the types of light chain subunits of the immunoglobulins with a molecular weight of approximately 22 kDa.
The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A family of double-stranded RNA-binding proteins that are related to NFATC TRANSCRIPTION FACTORS. In addition to binding to RNA, nuclear factor 90 proteins form heterodimeric complexes that regulate GENETIC TRANSCRIPTION and may play a role in T-CELL activation.
A membrane protein homologous to the ERM (Ezrin-Radixin-Moesin) family of cytoskeleton-associated proteins which regulate physical properties of membranes. Alterations in neurofibromin 2 are the cause of NEUROFIBROMATOSIS 2.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.
Tumor suppressor genes located on the long arm of human chromosome 22. Mutation or loss of these genes causes NEUROFIBROMATOSIS 2.
Genes encoding the different subunits of the IMMUNOGLOBULINS, for example the IMMUNOGLOBULIN LIGHT CHAIN GENES and the IMMUNOGLOBULIN HEAVY CHAIN GENES. The heavy and light immunoglobulin genes are present as gene segments in the germline cells. The completed genes are created when the segments are shuffled and assembled (B-LYMPHOCYTE GENE REARRANGEMENT) during B-LYMPHOCYTE maturation. The gene segments of the human light and heavy chain germline genes are symbolized V (variable), J (joining) and C (constant). The heavy chain germline genes have an additional segment D (diversity).
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results.
That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions.
Retroviral proteins that have the ability to transform cells. They can induce sarcomas, leukemias, lymphomas, and mammary carcinomas. Not all retroviral proteins are oncogenic.
Tumors or cancer of the PROSTATE.
Compounds based on benzeneacetamide, that are similar in structure to ACETANILIDES.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
A group of acylated oligopeptides produced by Actinomycetes that function as protease inhibitors. They have been known to inhibit to varying degrees trypsin, plasmin, KALLIKREINS, papain and the cathepsins.
A family of DNA binding proteins that regulate expression of a variety of GENES during CELL DIFFERENTIATION and APOPTOSIS. Family members contain a highly conserved carboxy-terminal basic HELIX-TURN-HELIX MOTIF involved in dimerization and sequence-specific DNA binding.
A component of NF-kappa B transcription factor. It is proteolytically processed from NF-kappa B p100 precursor protein and is important for maturation of B-LYMPHOCYTES and adaptive HUMORAL IMMUNITY.
The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (RECEPTORS, OPIOID, KAPPA) and have been shown to play a role as central nervous system transmitters.
Glycoproteins found on the membrane or surface of cells.
A group of viruses in the genus GAMMARETROVIRUS comprising a few isolates from birds, with no known corresponding endogenous relatives.
A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B and OSTEOPROTEGERIN. It plays an important role in regulating OSTEOCLAST differentiation and activation.
A member of the CXC chemokine family that plays a role in the regulation of the acute inflammatory response. It is secreted by variety of cell types and induces CHEMOTAXIS of NEUTROPHILS and other inflammatory cells.
A family of membrane-associated proteins responsible for the attachment of the cytoskeleton. Erythrocyte-related isoforms of ankyrin attach the SPECTRIN cytoskeleton to a transmembrane protein (ANION EXCHANGE PROTEIN 1, ERYTHROCYTE) in the erythrocyte plasma membrane. Brain-related isoforms of ankyrin also exist.
Transcriptional trans-acting proteins of the promoter elements found in the long terminal repeats (LTR) of HUMAN T-LYMPHOTROPIC VIRUS 1 and HUMAN T-LYMPHOTROPIC VIRUS 2. The tax (trans-activator x; x is undefined) proteins act by binding to enhancer elements in the LTR.
The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)
The major group of transplantation antigens in the mouse.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
A moderately firm, benign, encapsulated tumor resulting from proliferation of SCHWANN CELLS and FIBROBLASTS that includes portions of nerve fibers. The tumors usually develop along peripheral or cranial nerves and are a central feature of NEUROFIBROMATOSIS 1, where they may occur intracranially or involve spinal roots. Pathologic features include fusiform enlargement of the involved nerve. Microscopic examination reveals a disorganized and loose cellular pattern with elongated nuclei intermixed with fibrous strands. (From Adams et al., Principles of Neurology, 6th ed, p1016)
Any of the processes by which cytoplasmic factors influence the differential control of gene action in viruses.
ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known.
A class of opioid receptors recognized by its pharmacological profile. Mu opioid receptors bind, in decreasing order of affinity, endorphins, dynorphins, met-enkephalin, and leu-enkephalin. They have also been shown to be molecular receptors for morphine.
A class of opioid receptors recognized by its pharmacological profile. Delta opioid receptors bind endorphins and enkephalins with approximately equal affinity and have less affinity for dynorphins.
Systems of enzymes which function sequentially by catalyzing consecutive reactions linked by common metabolic intermediates. They may involve simply a transfer of water molecules or hydrogen atoms and may be associated with large supramolecular structures such as MITOCHONDRIA or RIBOSOMES.
A segment of the immunoglobulin heavy chains, encoded by the IMMUNOGLOBULIN HEAVY CHAIN GENES in the J segment where, during the maturation of B-LYMPHOCYTES; the gene segment for the variable region upstream is joined to a constant region gene segment downstream. The exact position of joining of the two gene segments is variable and contributes to ANTIBODY DIVERSITY. It is distinguished from the IMMUNOGLOBULIN J CHAINS; a separate polypeptide that serves as a linkage piece in polymeric IGA or IGM.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A kappa opioid receptor agonist. The compound has analgesic action and shows positive inotropic effects on the electrically stimulated left atrium. It also affects various types of behavior in mammals such as locomotion, rearing, and grooming.
An electrophoretic technique for assaying the binding of one compound to another. Typically one compound is labeled to follow its mobility during electrophoresis. If the labeled compound is bound by the other compound, then the mobility of the labeled compound through the electrophoretic medium will be retarded.
Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)
Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence.
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.
A group of disorders characterized by an autosomal dominant pattern of inheritance with high rates of spontaneous mutation and multiple neurofibromas or neurilemmomas. NEUROFIBROMATOSIS 1 (generalized neurofibromatosis) accounts for approximately 95% of cases, although multiple additional subtypes (e.g., NEUROFIBROMATOSIS 2, neurofibromatosis 3, etc.) have been described. (From Neurochirurgie 1998 Nov;44(4):267-72)
A type of neurofibroma manifesting as a diffuse overgrowth of subcutaneous tissue, usually involving the face, scalp, neck, and chest but occasionally occurring in the abdomen or pelvis. The tumors tend to progress, and may extend along nerve roots to eventually involve the spinal roots and spinal cord. This process is almost always a manifestation of NEUROFIBROMATOSIS 1. (From Adams et al., Principles of Neurology, 6th ed, p1016; J Pediatr 1997 Nov;131(5):678-82)
A family of proteins that are structurally-related to Ubiquitin. Ubiquitins and ubiquitin-like proteins participate in diverse cellular functions, such as protein degradation and HEAT-SHOCK RESPONSE, by conjugation to other proteins.
Any discrete, presumably solitary, mass of neoplastic PLASMA CELLS either in BONE MARROW or various extramedullary sites.
Glial cell derived tumors arising from the optic nerve, usually presenting in childhood.
Cis-acting regulatory sequences in the HIV long terminal repeat (LTR) which play a major role in induction or augmentation of HIV gene expression in response to environmental stimuli such as mitogens, phorbol esters, or other viruses. The HIV enhancer is the binding site for many cellular transcription factors including the nuclear factor NF-kappa B.
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.
Morphine derivatives of the methanobenzazocine family that act as potent analgesics.
Type III intermediate filament proteins that assemble into neurofilaments, the major cytoskeletal element in nerve axons and dendrites. They consist of three distinct polypeptides, the neurofilament triplet. Types I, II, and IV intermediate filament proteins form other cytoskeletal elements such as keratins and lamins. It appears that the metabolism of neurofilaments is disturbed in Alzheimer's disease, as indicated by the presence of neurofilament epitopes in the neurofibrillary tangles, as well as by the severe reduction of the expression of the gene for the light neurofilament subunit of the neurofilament triplet in brains of Alzheimer's patients. (Can J Neurol Sci 1990 Aug;17(3):302)
Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.
Deletion of sequences of nucleic acids from the genetic material of an individual.
An inducibly-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes and INFLAMMATION. It is the target of COX2 INHIBITORS.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.
Abnormal immunoglobulins characteristic of MULTIPLE MYELOMA.
A group of DITERPENES cyclized into 2-rings with a side-chain.
The phenomenon of immense variability characteristic of ANTIBODIES. It enables the IMMUNE SYSTEM to react specifically against the essentially unlimited kinds of ANTIGENS it encounters. Antibody diversity is accounted for by three main theories: (1) the Germ Line Theory, which holds that each antibody-producing cell has genes coding for all possible antibody specificities, but expresses only the one stimulated by antigen; (2) the Somatic Mutation Theory, which holds that antibody-producing cells contain only a few genes, which produce antibody diversity by mutation; and (3) the Gene Rearrangement Theory, which holds that antibody diversity is generated by the rearrangement of IMMUNOGLOBULIN VARIABLE REGION gene segments during the differentiation of the ANTIBODY-PRODUCING CELLS.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
A family of F-box domain proteins that contain sequences that are homologous to the beta subunit of transducin (BETA-TRANSDUCIN). They play an important role in the protein degradation pathway by becoming components of SKP CULLIN F-BOX PROTEIN LIGASES, which selectively act on a subset of proteins including beta-catenin and IkappaBbeta.
Transforming protein coded by jun oncogenes (GENES, JUN). This is a gag-onc fusion protein of about 65 kDa derived from avian sarcoma virus. v-jun lacks a negative regulatory domain that regulates transcription in c-jun.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
A secreted member of the TNF receptor superfamily that negatively regulates osteoclastogenesis. It is a soluble decoy receptor of RANK LIGAND that inhibits both CELL DIFFERENTIATION and function of OSTEOCLASTS by inhibiting the interaction between RANK LIGAND and RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
An inhibitor of SERINE ENDOPEPTIDASES. Acts as an alkylating agent and is known to interfere with the translation process.
A tumor necrosis factor receptor family member that is specific for RANK LIGAND and plays a role in bone homeostasis by regulating osteoclastogenesis. It is also expressed on DENDRITIC CELLS where it plays a role in regulating dendritic cell survival. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
Gated transport mechanisms by which proteins or RNA are moved across the NUCLEAR MEMBRANE.
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
Tricyclic ethylene-bridged naphthalene derivatives. They are found in petroleum residues and coal tar and used as dye intermediates, in the manufacture of plastics, and in insecticides and fungicides.
Substances that reduce or suppress INFLAMMATION.
A 15 kD "joining" peptide that forms one of the linkages between monomers of IMMUNOGLOBULIN A or IMMUNOGLOBULIN M in the formation of polymeric immunoglobulins. There is one J chain per one IgA dimer or one IgM pentamer. It is also involved in binding the polymeric immunoglobulins to POLYMERIC IMMUNOGLOBULIN RECEPTOR which is necessary for their transcytosis to the lumen. It is distinguished from the IMMUNOGLOBULIN JOINING REGION which is part of the IMMUNOGLOBULIN VARIABLE REGION of the immunoglobulin light and heavy chains.
A CALCIUM-independent subtype of nitric oxide synthase that may play a role in immune function. It is an inducible enzyme whose expression is transcriptionally regulated by a variety of CYTOKINES.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A cell-surface ligand involved in leukocyte adhesion and inflammation. Its production is induced by gamma-interferon and it is required for neutrophil migration into inflamed tissue.
A ubiquitously expressed sequence-specific transcriptional repressor that is normally the target of signaling by NOTCH PROTEINS.
Transcription factors that were originally identified as site-specific DNA-binding proteins essential for DNA REPLICATION by ADENOVIRUSES. They play important roles in MAMMARY GLAND function and development.
A large multinuclear cell associated with the BONE RESORPTION. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in CEMENTUM resorption.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.
One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla.
Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.
Inorganic compounds that contain gold as an integral part of the molecule.
A pattern recognition receptor that interacts with LYMPHOCYTE ANTIGEN 96 and LIPOPOLYSACCHARIDES. It mediates cellular responses to GRAM-NEGATIVE BACTERIA.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
A yellow-orange dye obtained from tumeric, the powdered root of CURCUMA longa. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes.
Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.
Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.
The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa.
A narcotic antagonist similar in action to NALOXONE. It is used to remobilize animals after ETORPHINE neuroleptanalgesia and is considered a specific antagonist to etorphine.
Antibodies produced by a single clone of cells.

Bcl-2 and Bcl-XL serve an anti-inflammatory function in endothelial cells through inhibition of NF-kappaB. (1/19220)

To maintain the integrity of the vascular barrier, endothelial cells (EC) are resistant to cell death. The molecular basis of this resistance may be explained by the function of antiapoptotic genes such as bcl family members. Overexpression of Bcl-2 or Bcl-XL protects EC from tumor necrosis factor (TNF)-mediated apoptosis. In addition, Bcl-2 or Bcl-XL inhibits activation of NF-kappaB and thus upregulation of proinflammatory genes. Bcl-2-mediated inhibition of NF-kappaB in EC occurs upstream of IkappaBalpha degradation without affecting p65-mediated transactivation. Overexpression of bcl genes in EC does not affect other transcription factors. Using deletion mutants of Bcl-2, the NF-kappaB inhibitory function of Bcl-2 was mapped to bcl homology domains BH2 and BH4, whereas all BH domains were required for the antiapoptotic function. These data suggest that Bcl-2 and Bcl-XL belong to a cytoprotective response that counteracts proapoptotic and proinflammatory insults and restores the physiological anti-inflammatory phenotype to the EC. By inhibiting NF-kappaB without sensitizing the cells (as with IkappaBalpha) to TNF-mediated apoptosis, Bcl-2 and Bcl-XL are prime candidates for genetic engineering of EC in pathological conditions where EC loss and unfettered activation are undesirable.  (+info)

Chlamydial and human heat shock protein 60s activate human vascular endothelium, smooth muscle cells, and macrophages. (2/19220)

Both chlamydial and human heat shock protein 60s (HSP 60), which colocalize in human atheroma, may contribute to inflammation during atherogenesis. We tested the hypothesis that chlamydial or human HSP 60 activates human endothelial cells (ECs), smooth muscle cells (SMCs), and monocyte-derived macrophages. We examined the expression of adhesion molecules such as endothelial-leukocyte adhesion molecule-1 (E-selectin), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), and the production of the proinflammatory cytokine interleukin-6 (IL-6). We also tested whether either HSP 60 induces nuclear factor-kappaB (NF-kappaB), which contributes to the gene expression of these molecules. Either chlamydial or human HSP 60 induced E-selectin, ICAM-1, and VCAM-1 expression on ECs similar to levels induced by Escherichia coli lipopolysaccharide (LPS). Each HSP 60 also significantly induced IL-6 production by ECs, SMCs, and macrophages to an extent similar to that induced by E. coli LPS, as assessed by enzyme-linked immunosorbent assay (ELISA). In ECs, either HSP 60 triggered activation of NF-kappaB complexes containing p65 and p50 Rel proteins. Heat treatment abolished all these effects, but did not alter the ability of E. coli LPS to induce these functions. Chlamydial and human HSP 60s therefore activate human vascular cell functions relevant to atherogenesis and lesional complications. These findings help to elucidate the mechanisms by which a chronic asymptomatic chlamydial infection might contribute to the pathophysiology of atheroma.  (+info)

B-MYB transactivates its own promoter through SP1-binding sites. (3/19220)

B-MYB is an ubiquitous protein required for mammalian cell growth. In this report we show that B-MYB transactivates its own promoter through a 120 bp segment proximal to the transcription start site. The B-MYB-responsive element does not contain myb-binding sites and gel-shift analysis shows that SP1, but not B-MYB, protein contained in SAOS2 cell extracts binds to the 120 bp B-myb promoter fragment. B-MYB-dependent transactivation is cooperatively increased in the presence of SP1, but not SP3 overexpression. When the SP1 elements of the B-myb promoter are transferred in front of a heterologous promoter, an increased response to B-MYB results. In contrast, c-MYB, the prototype member of the Myb family, is not able to activate the luciferase construct containing the SP1 elements. With the use of an SP1-GAL4 fusion protein, we have determined that the cooperative activation occurs through the domain A of SP1. These observations suggest that B-MYB functions as a coactivator of SP1, and that diverse combinations of myb and SP1 sites may dictate the responsiveness of myb-target genes to the various members of the myb family.  (+info)

Reactive oxygen intermediate-dependent NF-kappaB activation by interleukin-1beta requires 5-lipoxygenase or NADPH oxidase activity. (4/19220)

We previously reported that the role of reactive oxygen intermediates (ROIs) in NF-kappaB activation by proinflammatory cytokines was cell specific. However, the sources for ROIs in various cell types are yet to be determined and might include 5-lipoxygenase (5-LOX) and NADPH oxidase. 5-LOX and 5-LOX activating protein (FLAP) are coexpressed in lymphoid cells but not in monocytic or epithelial cells. Stimulation of lymphoid cells with interleukin-1beta (IL-1beta) led to ROI production and NF-kappaB activation, which could both be blocked by antioxidants or FLAP inhibitors, confirming that 5-LOX was the source of ROIs and was required for NF-kappaB activation in these cells. IL-1beta stimulation of epithelial cells did not generate any ROIs and NF-kappaB induction was not influenced by 5-LOX inhibitors. However, reintroduction of a functional 5-LOX system in these cells allowed ROI production and 5-LOX-dependent NF-kappaB activation. In monocytic cells, IL-1beta treatment led to a production of ROIs which is independent of the 5-LOX enzyme but requires the NADPH oxidase activity. This pathway involves the Rac1 and Cdc42 GTPases, two enzymes which are not required for NF-kappaB activation by IL-1beta in epithelial cells. In conclusion, three different cell-specific pathways lead to NF-kappaB activation by IL-1beta: a pathway dependent on ROI production by 5-LOX in lymphoid cells, an ROI- and 5-LOX-independent pathway in epithelial cells, and a pathway requiring ROI production by NADPH oxidase in monocytic cells.  (+info)

Activation-dependent transcriptional regulation of the human Fas promoter requires NF-kappaB p50-p65 recruitment. (5/19220)

Fas (CD95) and Fas ligand (CD95L) are an interacting receptor-ligand pair required for immune homeostasis. Lymphocyte activation results in the upregulation of Fas expression and the acquisition of sensitivity to FasL-mediated apoptosis. Although Fas upregulation is central to the preservation of immunologic tolerance, little is known about the molecular machinery underlying this process. To investigate the events involved in activation-induced Fas upregulation, we have examined mRNA accumulation, fas promoter activity, and protein expression in the Jurkat T-cell line treated with phorbol myristate acetate and ionomycin (P/I), pharmacological mimics of T-cell receptor activation. Although resting Jurkat cells express Fas, Fas mRNA was induced approximately 10-fold in 2 h upon P/I stimulation. Using sequential deletion mutants of the human fas promoter in transient transfection assays, we identified a 47-bp sequence (positions -306 to -260 relative to the ATG) required for activation-driven fas upregulation. Sequence analysis revealed the presence of a previously unrecognized composite binding site for both the Sp1 and NF-kappaB transcription factors at positions -295 to -286. Electrophoretic mobility shift assay (EMSA) and supershift analyses of this region documented constitutive binding of Sp1 in unactivated nuclear extracts and inducible binding of p50-p65 NF-kappaB heterodimers after P/I activation. Sp1 and NF-kappaB transcription factor binding was shown to be mutually exclusive by EMSA displacement studies with purified recombinant Sp1 and recombinant p50. The functional contribution of the kappaB-Sp1 composite site in P/I-inducible fas promoter activation was verified by using kappaB-Sp1 concatamers (-295 to -286) in a thymidine kinase promoter-driven reporter construct and native promoter constructs in Jurkat cells overexpressing IkappaB-alpha. Site-directed mutagenesis of the critical guanine nucleotides in the kappaB-Sp1 element documented the essential role of this site in activation-dependent fas promoter induction.  (+info)

Reduced phosphorylation of p50 is responsible for diminished NF-kappaB binding to the major histocompatibility complex class I enhancer in adenovirus type 12-transformed cells. (6/19220)

Reduced cell surface levels of major histocompatibility complex class I antigens enable adenovirus type 12 (Ad12)-transformed cells to escape immunosurveillance by cytotoxic T lymphocytes (CTL), contributing to their tumorigenic potential. In contrast, nontumorigenic Ad5-transformed cells harbor significant cell surface levels of class I antigens and are susceptible to CTL lysis. Ad12 E1A mediates down-regulation of class I transcription by increasing COUP-TF repressor binding and decreasing NF-kappaB activator binding to the class I enhancer. The mechanism underlying the decreased binding of nuclear NF-kappaB in Ad12-transformed cells was investigated. Electrophoretic mobility shift assay analysis of hybrid NF-kappaB dimers reconstituted from denatured and renatured p50 and p65 subunits from Ad12- and Ad5-transformed cell nuclear extracts demonstrated that p50, and not p65, is responsible for the decreased ability of NF-kappaB to bind to DNA in Ad12-transformed cells. Hypophosphorylation of p50 was found to correlate with restricted binding of NF-kappaB to DNA in Ad12-transformed cells. The importance of phosphorylation of p50 for NF-kappaB binding was further demonstrated by showing that an NF-kappaB dimer composed of p65 and alkaline phosphatase-treated p50 from Ad5-transformed cell nuclear extracts could not bind to DNA. These results suggest that phosphorylation of p50 is a key step in the nuclear regulation of NF-kappaB in adenovirus-transformed cells.  (+info)

Molecular mechanisms of constitutive NF-kappaB/Rel activation in Hodgkin/Reed-Sternberg cells. (7/19220)

A common characteristic of malignant cells derived from patients with Hodgkin's disease (HD) is a high level of constitutive nuclear NF-kappaB/Rel activity, which stimulates proliferation and confers resistance to apoptosis. We have analysed the mechanisms that account for NF-kappaB activation in a panel of Hodgkin/Reed-Sternberg (H-RS) cell lines. Whereas two cell lines (L428 and KMH-2) expressed inactive IkappaBalpha, no significant changes in NF-kappaB or IkappaB expression were seen in other H-RS cells (L591, L1236 and HDLM-2). Constitutive NF-kappaB was susceptible to inhibition by recombinant IkappaBalpha, suggesting that neither mutations in the NF-kappaB genes nor posttranslational modifications of NF-kappaB were involved. Endogenous IkappaBalpha was bound to p65 and displayed a very short half-life. IkappaBalpha degradation could be blocked by inhibitors of the NF-kappaB activating pathway. Proteasomal inhibition caused an accumulation of phosphorylated IkappaBalpha and a reduction of NF-kappaB activity in HDLM-2 and L1236 cells. By in vitro kinase assays we demonstrate constitutive IkappaB kinase (IKK) activity in H-RS cells, indicating ongoing signal transduction. Furthermore, H-RS cells secrete one or more factor(s) that were able to trigger NF-kappaB activation. We conclude that aberrant activation of IKK's, and in some cases defective IkappaBs, lead to constitutive nuclear NF-kappaB activity, which in turn results in a growth advantage of Hodgkin's disease tumor cells.  (+info)

Differential expression and translocation of protein tyrosine phosphatase 1B-related proteins in ME-180 tumor cells expressing apoptotic sensitivity and resistance to tumor necrosis factor: potential interaction with epidermal growth factor receptor. (8/19220)

Tumor necrosis factor (TNF)-induced apoptosis can be inhibited by overexpression of specific tyrosine kinases or activation of tyrosine kinase cascades, suggesting potential antagonism between apoptotic and tyrosine kinase signaling processes. In this report, the effects of TNF on EGF receptor tyrosine phosphorylation in ME-180 cell variants selected for apoptotic sensitivity (Sen) or resistance (Res) to TNF, previously shown to differentially express EGFr, were examined. Prior to the onset of apoptosis, TNF caused a significant reduction in the level of EGFr tyrosine phosphorylation in Sen cells but mediated only limited suppression of EGFr tyrosine phosphorylation in apoptotically resistant Res cells. In vitro incubation of cellular membranes with TNF derived from Sen cells stimulated a resident protein tyrosine phosphatase (PTP) activity which was able to dephosphorylate EGFr or tyrosine phosphopeptides mimicking an EGFr autophosphorylation site. In membrane preparations, PTPIB complexed with tyrosine phosphorylated EGFr and this association was disrupted by TNF through an apparent stimulation of PTP activity and turnover of phosphotyrosine. Intrinsic enzymatic activity of PTP1B was 2-3-fold higher in Sen versus Res cell lysates and a family of PTP1B-related proteins with altered C-termini was found to be highly expressed in Sen cells but absent or expressed at reduced levels in Res cells. Cytoplasmic extracts of Sen cells contained PTP1B-like proteins and TNF incubation resulted in the time dependent accumulation of PTP1B-like proteins in Sen cells but did not effect these proteins in Res cells. Together, these results suggest that specific changes in expression and subcellular distribution of phosphotyrosine modulatory proteins may play a role in conveying intrinsic apoptotic sensitivity to TNF in some tumor cell types.  (+info)

Nuclear factor-kappa B (NF-κB) is a ubiquitous transcription factor that is involved in inflammatory and immune responses, as well as in regulation of expression of many other genes related to cell survival, proliferation, and differentiation. In mammals, NF-κB comprises five subunits that can bind to promoter regions of target genes as homodimers or heterodimers. The most common dimer is the p50/p65 heterodimer. The several combinations of dimers that can be formed contribute to the heterogeneous regulation of NF-κB target genes, and this heterogeneity is further increased by interactions of the NF-κB dimers with other transcription factors, such as steroid hormone receptors, activator protein-1 (AP-1), and cAMP response element binding protein (CREB). In the thyroid, several studies have demonstrated the involvement of NF-κB in thyroid autoimmunity, thyroid cancer, and thyroid-specific gene regulation. The role of NF-κB in thyroid autoimmunity was hypothesized more than 20 years ago, after the
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NF-kappa B is a widely used regulator of inducible and tissue-specific gene control. In the cytosol, when complexed to an inhibitory molecule, I kappa B, NF-kappa B is in an inactive form and cannot bind DNA. Activation of cells with appropriate stimuli results in the dissociation of NF-kappa B from I kappa B and its translocation to the nucleus as an active binding protein. We now demonstrate that NF-kappa B binding in vitro can be inhibited by agents that modify free sulfhydryls. Binding is eliminated after treatment with N-ethylmaleimide, an alkylating agent, and diamide, an oxidizing agent. The diamide effect can be reversed by 2-mercaptoethanol. Further, 2-mercaptoethanol acts synergistically with deoxycholate plus Nonidet P-40 in converting inactive cytosolic NF-kappa B to an active DNA-binding form. It is therefore possible that modulation of the redox state of NF-kappa B could represent a post-translational control mechanism for this factor.. ...
TY - JOUR. T1 - Nuclear Role of IκB Kinase-γ/NF-κB Essential Modulator (IKKγ/NEMO) in NF-κB-dependent Gene Expression. AU - Verma, Udit N.. AU - Yamamoto, Yumi. AU - Prajapati, Shashi. AU - Gaynor, Richard B.. PY - 2004/1/30. Y1 - 2004/1/30. N2 - The IκB kinase (IKK) complex, which is composed of the two kinases IKKα and IKKβ and the regulatory subunit IKKγ/nuclear factor-κB (NF-κB) essential modulator (NEMO), is important in the cytokine-induced activation of the NF-κB pathway. In addition to modulation of IKK activity, the NF-κB pathway is also regulated by other processes, including the nucleocytoplasmic shuttling of various components of this pathway and the post-translational modification of factors bound to NF-κB-dependent promoters. In this study, we explored the role of the nucleocytoplasmic shuttling of components of the IKK complex in the regulation of the NF-κB pathway. IKKγ/NEMO was demonstrated to shuttle between the cytoplasm and the nucleus and to interact with the ...
The transcription factor nuclear factor-kappa B (NF-κB) plays an essential role in epidermal appendage induction and morphogenesis. In the epidermis of mice lacking NF-κB activity, initiation of primary hair follicle pre-placode formation is observed, but these primitive structures fail to proliferate and generate placodes. NF-κB signaling is known to modulate activity of WNT and SHH signaling at early stages of hair follicle development, but these roles do not fully account for the phenotypes observed when this pathway is blocked. To identify additional NF-κB target genes we developed a novel method to isolate and transcriptionally profile primary hair follicle placodes with active NF-κB signaling. In parallel, we compared gene expression at the same developmental stage in embryos with compromised NF-κB signaling, and wild type littermate controls. In addition to corroborating established NF-κB functions, these analyses uncovered novel NF-κB target genes with potential roles in priming ...
The transcriptional nuclear factor (NF)-kappaB can be activated by diverse stimuli such as cytokines, mitogens, oxidative stress, and lipids, leading to the transactivation of several genes that play important roles in the development of atherosclerosis. Because oxidative stress may play a key role in the pathogenesis of diabetic vascular disease, we have examined whether culture of porcine vascular smooth muscle cells (PVSMCs) under high glucose (HG) conditions (25 mmol/l) to simulate the diabetic state can lead to the activation of NF-kappaB, and also whether cytokine- or growth factor-induced NF-kappaB activation is altered by HG culture. We observed that PVSMCs cultured in HG showed significantly greater activation of NF-kappaB in the basal state compared with cells cultured in normal glucose (NG) (5.5 mmol/l). Treatment of the cells with cytokines, such as tumor necrosis factor (TNF)-alpha and interleukin-1beta, or with growth factors, such as platelet-derived growth factor, insulin-like ...
Todays study seeks to research the role of cathepsin L in glutamate receptor-induced transcription factor nuclear factor-kappa B (NF-B) activation and excitotoxicity in rats striatal neurons. degradation and phosphorylation, adjustments in the degrees of IKK, p-IKK, TP53, caspase-3, beclin1, p62, and LC3II/LC3I. The results show that QA-induced lack of striatal neurons were inhibited by Z-FF-FMK […]. Read More ». ...
Todays study seeks to research the role of cathepsin L in glutamate receptor-induced transcription factor nuclear factor-kappa B (NF-B) activation and excitotoxicity in rats striatal neurons. degradation and phosphorylation, adjustments in the degrees of IKK, p-IKK, TP53, caspase-3, beclin1, p62, and LC3II/LC3I. The results show that QA-induced lack of striatal neurons were inhibited by Z-FF-FMK […]. Read More ». ...
Around 40,000 people die from sepsis in the UK each year. Although the Surviving Sepsis Campaign -a performance improvement effort by hospitals across Europe, South America and the United States- has improved outcomes, the mortality rate remains at 31% overall, and ,70% in patients who develop sepsis-induced multiple organ failure.. Oxidative stress in patients with sepsis has been consistently described over the last 20 years by us and others (reviewed in [2]). Oxidative stress initiates inflammatory responses via activation of the redox sensitive transcription factor nuclear factor kappa B (NFkB). Mitochondrial dysfunction initiated by oxidative stress is generally accepted as a playing a major role in sepsis induced organ failure.. Production of energy takes place in mitochondria resulting in production of reactive oxygen species (ROS) as by-products. Although ROS are damaging, they are essential in cell signalling and their activity is tightly regulated by a network of antioxidants. When ...
Objective-The activation of nuclear factor-kB (NF-kB) is a crucial step in the arterial walls response to injury. The identification and characterization of the NF-kB essential modulator- binding domain (NBD) peptide, which can block the activation of the IkB kinase complex, have provided an opportunity to selectively abrogate the inflammation-induced activation of NF-kB. The aim of the present study was to evaluate the effect of the NBD peptide on neointimal formation.,br,,/br, Methods and Results-In the rat carotid artery balloon angioplasty model, local treatment with the NBD peptide (300 microg/site) significantly reduced the number of proliferating cells at day 7 (by 40%; P,0.01) and reduced injury-induced neointimal formation (by 50%; P,0.001) at day 14. These effects were associated with a significant reduction of NF-kB activation and monocyte chemotactic protein-1 expression in the carotid arteries of rats treated with the peptide. In addition, the NBD peptide (0.01 to 1 micromol/L) ...
TY - JOUR. T1 - Cytosolic-DNA-mediated, STING-dependent proinflammatory gene induction necessitates canonical NF-kB activation through TBK1. AU - Abe, Takayuki. AU - Barber, Glen N.. PY - 2014. Y1 - 2014. N2 - STING (stimulator of interferon genes) is known to control the induction of innate immune genes in response to the recognition of cytosolic DNA species, including the genomes of viruses such as herpes simplex virus 1 (HSV-1). However, while STING is essential for protection of the host against numerous DNA pathogens, sustained STING activity can lead to lethal inflammatory disease. It is known that STING utilizes interferon regulatory factor 3 (IRF3) and nuclear factor kB (NF-kB) pathways to exert its effects, although the signal transduction mechanisms remain to be clarified fully. Here we demonstrate that in addition to the activation of these pathways, potent induction of the Jun N-terminal protein kinase/stress-activated protein kinase (JNK/SAPK) pathway was similarly observed in ...
Fischer, J.G.; Glauert, H.P.; Yin, T., 2002: Moderate Iron Overload Enhances Lipid Peroxidation in Livers of Rats, but Does Not Affect NF-kB Activation Induced by the Peroxisome Proliferator, Wy-14,643
AIMS/HYPOTHESIS: The beta cell destruction and insulin deficiency that characterises type 1 diabetes mellitus is partially mediated by cytokines, such as IL-1beta, and by nitric oxide (NO)-dependent and -independent effector mechanisms. IL-1beta activates mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), p38 and c-Jun NH2-terminal kinase (JNK), and the nuclear factor kappa B (NFkappaB) pathway. Both pathways are required for expression of the gene encoding inducible nitric oxide synthase (iNOS) and for IL-1beta-mediated beta cell death. The molecular mechanisms by which these two pathways regulate beta cell Nos2 expression are currently unknown. Therefore, the aim of this study was to clarify the putative crosstalk between MAPK and NFkappaB activation in beta cells. MATERIALS AND METHODS: The MAPKs ERK, p38 and JNK were inhibited by SB203580, PD98059 or Tat-JNK binding domain or by cells overexpressing the JNK binding domain. The effects
Negative selection eliminates thymocytes bearing autoreactive T cell receptors (TCR) via an apoptotic mechanism. We have cloned an inhibitor of NF-kappa B, I kappa BNS, which is rapidly expressed upon TCR-triggered but not dexamethasone- or gamma irradiation-stimulated thymocyte death. The predicted protein contains seven ankyrin repeats and is homologous to I kappa B family members. In class I and class II MHC-restricted TCR transgenic mice, transcription of I kappa BNS is stimulated by peptides that trigger negative selection but not by those inducing positive selection (i.e., survival) or nonselecting peptides. I kappa BNS blocks transcription from NF-kappa B reporters, alters NF-kappa B electrophoretic mobility shifts, and interacts with NF-kappa B proteins in thymic nuclear lysates following TCR stimulation. Retroviral transduction of I kappa BNS in fetal thymic organ culture enhances TCR-triggered cell death consistent with its function in selection.. ...
en] The role of nuclear factor (NF)-kappa B in the regulation of apoptosis in normal and cancer cells has been extensively studied in recent years. Constitutive NF-kappa B activity in B lymphocytes as well as in Hodgkins disease and breast cancer cells protects these cells against apoptosis. It has also been reported that NF-kappa B activation by tumor necrosis factor (TNF)-alpha, chemotherapeutic drugs, or ionizing radiations can protect several cell types against apoptosis, suggesting that NF-kappa B could participate in resistance to cancer treatment. These observations were explained by the regulation of antiapoptotic gene expression by NF-kappa B. However, in our experience, inhibition of NF-kappa B activity in several cancer cell lines has a very variable effect on cell mortality, depending on the cell type, the stimulus, and the level of NF-kappa B inhibition. Moreover, in some experimental systems, NF-kappa B activation is required for the onset of apoptosis. Therefore, it is likely ...
Title: Molecular Mechanisms of Bcl10-Mediated NF-kappaB Signal Transduction Author: Felicia D. Langel, Ph.D., 2006 Directed by: Brian C. Schaefer, Ph.D., Assistant Professor, Department of Microbiology and Immunology Bcl10 is a key signaling intermediate in the TCR-to-NF-?B pathway in T lymphocytes. It is currently believed that, once activated, Bcl10 functions within a multiprotein signaling complex that activates the IKK complex. Bcl10 is thought to regulate this signaling complex, but how it transmits its signal through the complex is unknown. A thorough knowledge of Bcl10 biology is critical to understanding how Bcl10 functions and how it regulates its binding partners. In this study, we used mutational analysis, molecular imaging, biochemistry, and computer/bioinformatics modeling to elucidate a structure and function for Bcl10. From our data, we identified a novel binding site for MALT1 within the Bcl10 protein, hypothesized that this site is completely separate and distinct from the ...
The sequence and biochemical properties of the product of the cloned cDNA for the p65 subunit of nuclear factor kappa B (NF-kappa B) have been determined. The cDNA has an open reading frame of 549 amino acids capable of encoding a 60 kd protein. NF-kappa B p65 contains an amino-terminal region of 320 amino acids with extensive similarity to the oncogene c-rel and lesser similarity to NF-kappa B p50. In vitro translated p65 forms a DNA-binding complex with NF-kappa B p50, and the binding of this complex can be specifically inhibited by purified I kappa B. Progressive carboxy-terminal deletions of p65 show that, contrary to previous assumptions, p65 does include a DNA-binding domain that in vivo might become activated only through hetero-oligomerization with p50. DNA binding by truncated p65 is inhibited by I kappa B, thus mapping the I kappa B interaction domain to the rel-homologous region and suggesting that I kappa B exerts its inhibitory effect upon NF-kappa B primarily through interaction with p65.
In contrast, compared to NTG HF, TG HF hearts had markedly reduced (p , 0.01) NF-κB DNA activation, and significantly less (p , 0.05) LV dilatation (LVEDV 52 ± 20 μL) and systolic dysfunction (LVEF 61 ± 8 %), but a similar degree of hypertrophy as assessed by LV/TL and ANF expression. Moreover, as compared to TG sham, TG HF hearts exhibited no TNF, IL-1β, or IL-6 upregulation. Importantly, as compared to TG sham, TG HF showed only a mild increase in apoptotic rate (0.4 ± 0.3 %) that was not statistically significant (p = 0.45), suggesting that differences in the rate of cell loss between NTG and TG HF may account for comparable degrees of chamber hypertrophy despite differences in LV dilatation.. Conclusion: Persistent NF-κB activation imparts detrimental effects in post-infarction HF and worsens LV remodeling, related, at least in part, to augmentation of inflammatory cytokine expression and apoptosis. ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) refers to a protein complex functional in signaling pathways, particularly in response to stress stimuli. There are two signaling pathways leading to the activation of NF-kB signaling, known as the canonical (or classical) pathway, the non-canonical (or alternative) pathway.. In the canonical NF-kB pathway, NF-kB dimers such as p50/RelA are maintained in the cytoplasm by interaction with an independent Inhibitor of NF-kB (IkB) molecule. When the upstream signaling is active, an IkBa kinase (IKK) complex consisting of catalytic kinase subunits IKKa and/or IKKb and the scaffold protein NEMO will be recruited to the cytoplasmic adaptor of certain cell surface receptor and stay activated. Activation of IKK complex will consequently phosphorylate the IkB at two serine residues, which induce the proteasomal degradation of IkB. Released from IkB, NF-kB dimers then translocate into the nucleus and bind with a consensus sequence ...
In this review poster, we researched the function, regulation, and structure of NF-κB as it relates to carcinogenesis. Found in almost all animal cells, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a transcription factor that plays various roles in cellular proliferation, cell survival, inflammation, and T cell activation. There are two different NF-κB signaling pathways: the canonical pathway and the non-canonical pathway. NF-κB forms a p50/Rel A heterodimer in the canonical pathway and a p52/ Rel B heterodimer in the non-canonical pathway. NF-κB protein is normally sequestered in the cytoplasm as an inactive complex with a κB inhibitor (IκB) protein. Outside stimuli such as reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF-α) activate cell surface receptors such as Toll-Like Receptors (TLRs) and Receptor Activators of NF-κB (RANK). These surface receptors, in turn, activate IκB kinase (IKK). IKK phosphorylates IκB, which causes ...
Being naturally curious necessitates spending time for more discovery. This statement holds true in the presence of the conduit and the means for gathering information. As I was curious reading about bee venom and its potential role in targeting tumors, I encountered NF-kB, which I already did encounter it long ago in my virology and immunology classes.. I needed a refresh, so I sought for papers that could help me with that.. What is NF-kB again? It is the nuclear factor kappa-light-chain-enhancer of activated B cells (thats mouthful). It has so many roles, namely in cellular growth, immunity, and oncogenesis. It is a transcription factor that upon activation through phosphorylation by the IKK (IkB kinase) protein, it will go into nucleus and bind to specific DNA sequence.. In its inactive state, it is sequestered in the cytoplasm of a cell. It is sequestered by having its nuclear localization signals masked by a protein called IkB. Thus activation of NF-kB is resulted from the degradation of ...
Previous investigations suggest that DL-3-n-butylphthalide (NBP) is a promising multifaceted drug for the treatment of stroke. It is not clear whether NBP can treat traumatic brain injury (TBI) and what could be the mechanisms of therapeutic benefits. To address these issues, TBI was induced by a controlled cortical impact in adult male mice. NBP (100 mg/kg) or saline was intraperitoneally administered within 5 min after TBI. One day after TBI, apoptotic events including caspase-3/9 activation, cytochrome c release from the mitochondria, and apoptosis-inducing factor (AIF) translocation into the nucleus in the pericontusion region were attenuated in NBP-treated mice compared to TBI-saline controls. In the assessment of the nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) pathway, NBP ameliorated the p65 expression and the p-IκB-α/IκB-α ratio, indicating reduced NF-κB activation. Consistently, NBP reduced the upregulation of proinflammatory cytokines such as tumor ...
DNA transcription control. Computer model showing a molecule of the FP50 homodimer (green) from NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) bound to the DNA interferon regulatory factor (IRF) recognition sequence on a strand of DNA (deoxyribonucleic acid, orange). NF-kB is a protein complex that controls the transcription of DNA. IRFs are proteins that regulate the transcription of interferons, which are released in response to the presence of pathogens. - Stock Image C010/4990
Nuclear factor-kappa B (NF-kappa B) transcription factors represent a conserved family of proteins that regulate not only immune cells, but also heart cells, glial cells and neurons, playing a fundamental role in various cellular processes. Due to its dysregulation in certain cancer types as well as in chronic inflammation and autoimmune diseases, it has recently been appreciated as an important therapeutic target. The aim of this study was to investigate the binding pocket of NF-kappa B (p50/p65) heterodimer complex in association with NF-kappa B inhibitor I kappa B alpha to identify potent ligands via fragment-based e-pharmacophore screening. The ZINC Clean Fragments (similar to 2 million) and the Schrodingers medically relevant Glide fragments library (similar to 670) were used to create the e-pharmacophore models at the potential binding site which was validated by site mapping. Glide/HTVS docking was conducted followed by re-docking of the top 20% fragments by Glide/SP and Glide/XP ...
Statement from paper: To test whether RIP3 and RIP4 have to be ubiquitinated by cIAP1/2 in order to mediate NF-kB activation, we compared RIP-mediated NF-kB luciferase reporter activity when ectopically expressed in HEK293T cells in the presence or absence of the IAP inhibitor BV6, a treatment that induces rapid auto-ubiquitination and degradation of endogenous cIAP1/2[41]. As shown in Figure 4A, BV6 treatment greatly impaired TNF and RIP1 RIP4-induced NF-kB activation but had no impact on TAK1-mediated NF-kB induction (Figure 4A). Those results, which indicate that cIAP1/2 act upstream of TAK1, are consistent with a role for cIAP1/2 as E3 ligases regulating RIP14-mediated activation of NF-kB. Expressed in LEGO: http://go-genkisugi.rhcloud.com/seed/model/gomodel:taxon_9606-5408ded30000003 previous recommendation RIP3: GO:0051092 positive regulation of NF-kappaB transcription factor activity: PMID:21931591: dependent_on(UniProtKB:Q13490 IAP2) Ruth comment: this highlights the problem of ...
Neuroinflammation is an essential defense response to pathogens or injury in the central nervous system, but might also contribute to the pathogenesis of neurological disorders. Astrocytes are glial cells that are implicated in neuroinflammation, but also in brain development and homeostasis. The NF-kappa B transcription factors are key regulators of inflammation that also regulate in cell proliferation, differentiation and survival. Previous studies suggested that NF-kappa B activation in astrocytes might indeed be critical for neuroinflammatory responses and its pathological consequences. In the present study a novel mouse model was characterized to further elucidate the role of astroglial NF-Kappa B signaling in neuroinflammation. This model conditionally expresses a constitutively active mutant of the NF-kappa B activating kinase IKK2 in astrocytes. This results in astroglial NF-kappa B activation, which is sufficient to induce a prominent neuroinflammatory response and impairs brain ...
Neuroinflammation is an essential defense response to pathogens or injury in the central nervous system, but might also contribute to the pathogenesis of neurological disorders. Astrocytes are glial cells that are implicated in neuroinflammation, but also in brain development and homeostasis. The NF-kappa B transcription factors are key regulators of inflammation that also regulate in cell proliferation, differentiation and survival. Previous studies suggested that NF-kappa B activation in astrocytes might indeed be critical for neuroinflammatory responses and its pathological consequences. In the present study a novel mouse model was characterized to further elucidate the role of astroglial NF-Kappa B signaling in neuroinflammation. This model conditionally expresses a constitutively active mutant of the NF-kappa B activating kinase IKK2 in astrocytes. This results in astroglial NF-kappa B activation, which is sufficient to induce a prominent neuroinflammatory response and impairs brain ...
The Tumor Necrosis Factor (TNF) Receptor Associated Factor 6 (TRAF6) is an intracellular signal transducers, being responsible for mediating many of the activation events initiated by TNF receptor (TNFR) and Toll-like/Interleukin-1 and 18 receptor (TIR) families, in which TRAF6 plays central roles in numerous biological processes including innate and adaptive immunity, osteoclastogenesis and bone development, CD40 signaling, neuronal cell development, and cancer cell progression. Acting as an E3 ubiquitin ligase, TRAF6 catalyzes lysine 63 linked poly-ubiquitination of itself and many other signal transducers upon association with upstream effectors possessing a short TRAF Interaction Motif (TIM) peptide sequence in the NF-KappaB signal transduction pathway. Ectopic over-expression of TRAF6 acts as a dominant-positive. However, the mechanism of TRAF6 activation by upstream activators or over-expression is unclear. This motivated our enthusiasm to study the role played by ubiquitination for TRAF6 in NF
Nuclear factor-kappa B (NF-kappaB) is an important transcription factor, involved in many immune and inflammatory responses. It is critical in HIV gene expression as it has kappa B binding sites in the HIV-1 long-terminal repeat. Hence, targeting NF-kappaB to prevent its DNA binding holds a signific …
The May laboratory investigates signal transduction pathways that lead to altered patterns of gene expression in immune and inflammatory responses. We are particularly interested in understanding how the loss of control of normal signaling contributes to the progression of diseases such as chronic inflammation and cancer. Our goal is to determine the specific molecular events underlying aberrant signals and to define realistic targets for selectively blocking abnormal, while maintaining physiologically normal responses. The focus of our work is the Nuclear Factor (NF)-kappa B transcription factor activation pathway that is critical for inflammation, innate and adaptive immunity and lymphocyte development. NF-kappa B activation is typically a rapid and transient response, however constitutive NF- kappa B activity occurs at sites of chronic inflammation and in various tumors, leukemias and lymphomas. We combine cellular, molecular and genetic approaches to determine the mechanisms that redirect ...
Increasing evidence from epidemiological, preclinical and clinical studies suggests that dysregulated inflammatory response plays a pivotal role in a multitude of chronic ailments including cancer. The molecular mechanism(s) by which chronic inflammation drives cancer initiation and promotion include increased production of pro-inflammatory mediators, such as cytokines, chemokines, reactive oxygen intermediates, increased expression of oncogenes, COX-2 (cyclo-oxygenase-2), 5-LOX (5-lipoxygenase) and MMPs (matrix metalloproteinases), and pro-inflammatory transcription factors such as NF-κB (nuclear factor κB), STAT3 (signal transducer and activator of transcription 3), AP-1 (activator protein 1) and HIF-1α (hypoxia-inducible factor 1α) that mediate tumour cell proliferation, transformation, metastasis, survival, invasion, angiogenesis, chemoresistance and radioresistance. These inflammation-associated molecules are activated by a number of environmental and lifestyle-related factors including ...
Danger signals activate Toll-like receptors (TLRs), thereby initiating inflammatory responses. Canonical TLR signalling, via Toll/Interleukin-1 receptor domain (TIR)-containing adaptors and proinflammatory transcription factors such as NF-κB, occurs in many cell types; however, additional mechanisms are required for specificity of inflammatory responses in innate immune cells. Here we show that SCIMP, an immune-restricted, transmembrane adaptor protein (TRAP), promotes selective proinflammatory cytokine responses by direct modulation of TLR4. SCIMP is a non-TIR-containing adaptor, binding directly to the TLR4-TIR domain in response to lipopolysaccharide. In macrophages, SCIMP is constitutively associated with the Lyn tyrosine kinase, is required for tyrosine phosphorylation of TLR4, and facilitates TLR-inducible production of the proinflammatory cytokines IL-6 and IL-12p40. Point mutations in SCIMP abrogating TLR4 binding also prevent SCIMP-mediated cytokine production. SCIMP is, therefore, an immune
Members of the NF-kappa B/Rel transcription factor family have been shown recently to be required for cellular transformation by oncogenic Ras and by other oncoproteins and to suppress transformation-associated apoptosis. Furthermore, NF-kappa B has been shown to be activated by several oncoproteins …
Among the many target genes of the transcription factor NF-kappaB are p53 and c-myc, both of which are involved in apoptosis. This prompted us to investigate the role of NF-kappaB in this process. We report that NF-kappaB is potently activated upon serum starvation, a condition leading to apoptosis in 293 cells. Similar to Bcl-2, a transdominant-negative mutant of the NF-kappaB p65 subunit partially inhibited apoptosis, indicating a direct involvement of the transcription factor in induction of cell death. As expected, the p65 mutant suppresses kappaB-dependent gene expression. Surprisingly, transiently or stably overexpressed Bcl-2 had the same effect. The transcription inhibitory activity of the two proteins correlated with their cell death protective potential. Like Bcl-2, the related protein Bcl-xL but not Bcl-xS was able to suppress kB-dependent transcription. Bcl-2 inhibited NF-kappaB activity by an unusual mechanism. It did not prevent the release of IkappaB in the cytoplasm but ...
Death receptor 6 (DR6, TNFRSF21) is a member of the death receptor family, which belongs to the superfamily of tumor necrosis factor receptors.
Tumour necrosis factor (p55 or p60) receptor (TNFR) 1 is the major receptor that activates pro-inflammatory signalling and induces gene expression in response to TNF. Consensus is lacking for the function of (p75 or p80) TNFR2 but experiments in mice have suggested neuro-, cardio- and osteo-protective and anti-inflammatory roles. It has been shown in various cell types to be specifically required for the induction of TNFR-associated factor-2 (TRAF2) degradation and activation of the alternative nuclear factor (NF)-kappaB pathway, and to contribute to the activation of mitogen-activated protein kinases (MAPK) and the classical NF-kappaB pathway. We have investigated the signalling functions of TNFR2 in primary human and murine macrophages. We find that in these cells TNF induces TRAF2 degradation, and this is blocked in TNFR2(-/-) macrophages. TRAF2 has been previously reported to be required for TNF-induced activation of p38 MAPK. However, TRAF2 degradation does not inhibit TNF-induced tolerance of p38
Cross-species comparison revealed that conservation of NF-κB family - related TFBS motifs is much higher in the Early genes group than in the Late genes group. The highest numbers of common DNA binding motifs considered were found in the locations where the adjusted promoter sequences were highly conserved. For almost all Early genes, the NF-κB-family related TFBS motifs were conserved between most pairs of species, with the exception of comparison between mouse and cattle in TNF. As we presumed the best promoter sequence conservation and interspecies conservation of TF binding motifs persisted between human and chimp, followed in many cases by that between human and cattle. In the case of two Early genes, REL and TNFAIP3 comparison, no conserved NF-κB-family related TFBS were found between chimpanzee or mouse and cattle. In human versus cattle comparison two single non-overlapping binding sites were found, but this is a low score in comparison with the number of conserved TFBS found in other ...
Phosphorylation of RELA plays a key role in regulating NF-κB activation and function. Subsequent to NF-κB nuclear translocation, RELA undergoes site-specific post-translational modifications to further enhance the NF-κB function as a transcription factor. RELA can either be phosphorylated in the RHD region or the TAD region, attracting different interaction partners. Triggered by lipopolysaccharide (LPS), protein kinase A (PKA) specifically phosphorylates serine 276 in the RHD domain in the cytoplasm, controlling NF-κB DNA-binding and oligomerization.[6] On the other hand, mitogen and stress-activated kinase 1 (MSK1) are also able to phosphorylate RELA at residue 276 under TNFα induction in the nucleus, increasing NF-κB response at the transcriptional level.[7] Phosphorylation of serine 311 by protein kinase C zeta type (PKCζ) serves the same purpose.[8] Two residues in the TAD region are targeted by phosphorylation. After IL-1or TNFα stimulation, serine 529 is phosphorylated by casein ...
The aim of the studies described in this thesis was to investigate the development of experimental hereditary hypertension and to persistently ameliorate the development of hypertension due brief interventions during early development (perinatal treatment). We used two different models of experimental hereditary hypertension, namely the spontaneously hypertensive rat (SHR) and ... read more the fawn-hooded hypertensive rat (FHH). SHR and FHH dams and their offspring were supplemented with five different treatments during pregnancy and lactation. We found that in both models the perinatal manipulation on the balance between nitric oxide (NO) and reactive oxygen species, with L-arginine and antioxidants, resulted in a persistent decrease in blood pressure and prevented renal injury in the FHH. A similar effect was found after perinatal inhibition of the inflammatory transcription factor NF-kappaB. With micoarray analysis we investigated the transcriptome throughout life in SHR and we developed a ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Cyclooxygenase-2 (COX-2) is an inducible enzyme that drives inflammation and is the therapeutic target for widely used nonsteroidal antiinflammatory drugs (NSAIDs). However, COX-2 is also constitutively expressed, in the absence of overt inflammation, with a specific tissue distribution that includes the kidney, gastrointestinal tract, brain, and thymus. Constitutive COX-2 expression is therapeutically important because NSAIDs cause cardiovascular and renal side effects in otherwise healthy individuals. These side effects are now of major concern globally. However, the pathways driving constitutive COX-2 expression remain poorly understood. Here we show that in the kidney and other sites, constitutive COX-2 expression is a sterile response, independent of commensal microorganisms and not associated with activity of the inflammatory transcription factor NF-κB. Instead, COX-2 expression in the kidney but not other regions colocalized with nuclear factor of activated T cells (NFAT) transcription ...
BACKGROUND: The zinc finger protein A20 is an ubiquitinating/deubiquitinating enzyme essential for the termination of inflammatory reactions through the inhibition of nuclear factor kappaB (NF-kappaB) signaling. Moreover, it also shows anti-apoptotic activities in some cell types and proapoptotic/pronecrotic effects in others. Although it is known that the regulation of inflammatory and cell death processes are critical in proper brain functioning and that A20 mRNA is expressed in the CNS, its role in the brain under physiological and pathological conditions is still unknown. METHODS: In the present study, we have evaluated the effects of A20 overexpression in mixed cortical cultures in basal conditions: the in vivo pattern of endogenous A20 expression in the control and N-methyl-d-aspartate (NMDA) excitotoxically damaged postnatal day 9 immature rat brain, and the post-injury effects of A20 overexpression in the same lesion model. RESULTS: Our results show that overexpression of A20 in mixed cortical
Nuclear factor kappa B (NF-κB) is a transcription factor that is associated with inflammation. Without stimulus, NF-κB is repressed by inhibitor of kappa B (IκB) proteins. Upon stimulation by TNF, IL-1, and/or pathogen-associated molecular patterns (e.g. LPS), adaptor proteins like MyD88 and TRAF will signal for the activation of inhibitor of kappa B kinase (IκBK), which goes on to phosphorylate either IκB (canonical pathway) or the p100 subunit of NF-κB (alternative pathway). The pathway of activation is dictated by the signal: TNF, IL-1 and TLR stimulation activate the classical pathway, while CD40L and BAFF activate the alternative pathway. In the classical pathway, phosphorylated IκB is ubiquitinated and then degraded, allowing for NF-κB to enter the nucleus and turn on transcription of genes for cytokines like TNFα and IL-1. The alternative pathway involves activation of the NF-κB-inducing kinase (NIK), which turns on IκB kinase-α (IKKα), leading to p100 phosphorylation.. Click ...
E3330 (APX-3330) is a direct, orally active AP endonuclease 1 (APE1; also known as REF-1) inhibitor, which suppresses NF-κB DNA-binding activity. E3330 (APX-3330) blocks TNF-α-induced activation of IL-8 production in liver cancer cell lines. E3330 (APX-3330) shows anticancer properties, such as inhibition of cancer cell growth and migration. - Mechanism of Action & Protocol.
Induction of apoptosis and NF-kB activation by Apaf-1/Nod1 family members and DD proteins (Inohara et al., 2000). The more recent study suggested that IKKgamma binds to the site in C-terminal regulatory region of IKKbeta which is located after the HLH motif. Images ...
PMID 15459013] Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor-kappaB activation: common genetic etiology with Blau syndrome. ...
The nuclear factor-kappaB (NF-kappaB) transcription factors have emerged as major regulators of programmed cell death (PCD) whether via apoptosis or necrosis. In this context, NF-kappaBs activity has important ramifications for normal tissue development, homoeostasis and the physiological functions of various cell systems including the immune, hepatic, epidermal and nervous systems. However, improper regulation of PCD by NF-kappaB can have severe pathologic consequences, ranging from neurodegeneration to cancer, where its activity often precludes effective therapy. Although NF-kappaB generally protects cells by inducing the expression genes encoding antiapoptotic and antioxidizing proteins, its role in apoptosis and necrosis can vary markedly in different cell contexts, and NF-kappaB can sensitize cells to death-inducing stimuli in some instances. This article describes our current knowledge of the role of NF-kappaB in apoptosis and necrosis, and focuses on the many advances since we last ...
Relative abundance of full-length and truncated FOXP1 isoforms is associated with differential NFkappaB activity in Follicular Lymphoma. Leuk Res. 2009 Dec; 33(12):1699-702 ...
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BACKGROUND: Unloading of skeletal muscle causes atrophy and loss of contractile function. In part, this response is believed to be mediated by the transcription factor nuclear factor-kappa B (NF-kappaB). Both curcumin, a component of the spice turmeric, and N-acetylcysteine (NAC), an antioxidant, inhibit activation of NF-kappaB by inflammatory stimuli, albeit by different mechanisms. In the present study, we tested the hypothesis that dietary curcumin or NAC supplementation would inhibit unloading-induced NF-kappaB activity in skeletal muscle and thereby protect muscles against loss of mass and function caused by prolonged unloading. METHODS: We used hindlimb suspension to unload the hindlimb muscles of adult mice. Animals had free access to drinking water or drinking water supplemented with 1% NAC and to standard laboratory diet or diet supplemented with 1% curcumin. For 11 days, half the animals in each dietary group were suspended by the tail (unloaded) and half were allowed to ambulate freely.
Humans are symbiotic organisms; our genome is populated with a substantial number of endogenous retroviruses (ERVs), some remarkably intact, while others are remnants of their former selves. Current research indicates that not all ERVs remain silent passengers within our genomes; re-activation of ERVs is often associated with inflammatory diseases. ERVK is the most recently endogenized and transcriptionally active ERV in humans, and as such may potentially contribute to the pathology of inflammatory disease. Here, we showcase the transcriptional regulation of ERVK. Expression of ERVs is regulated in part by epigenetic mechanisms, but also depends on transcriptional regulatory elements present within retroviral long terminal repeats (LTRs). These LTRs are responsive to both viral and cellular transcription factors; and we are just beginning to appreciate the full complexity of transcription factor interaction with the viral promoter. In this review, an exploration into the inflammatory transcription
Objective-Pleiotropic atheroprotective effects of HMG-CoA reductase inhibitors may be mediated on the level of vascular gene transcription. The aim of this study was to characterize the effects of statins on the activation of transcription factors known to regulate inflammation and cell proliferation/differentiation. Methods and Results-Simvastatin, atorvastatin, and lovastatin (0.1 to 10 mumol/L) inhibited the binding of nuclear proteins to both the nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) DNA consensus oligonucleotides in human endothelial and vascular smooth muscle cells as assessed by electrophoretic mobility shift assay (EMSA). The inhibitory effects of statins on NF-kappaB or AP-1-dependent transcriptional activity were examined by transient transfection studies. HMG-CoA reductase inhibitors upregulated IkappaB-alpha protein levels in endothelial cells and decreased c-Jun mRNA expression in smooth muscle cells as analyzed by Western and Northern blotting, ...
NF-kappa B, a master regulator of several signaling cascades, is known to be actively transported in the nucleus in response to various stimuli. Here, we found that NF-kappa B is associated with polymeric tubulin and co-localized with microtubules in MCF-7 cells. Using TN16, a known microtubule targeting agent, we found that microtubule dynamics plays a critical role in NF-kappa B-microtubule interaction. Treatment of cells with low concentrations of TN16 (25 and 50 nM) that suppressed microtubule dynamics without visibly affecting microtubule organization enhanced the association of NF-kappa B with microtubules and facilitated nuclear translocation of NF-kappa B. Colchicine and vinblastine also produced similar nuclear translocation of NF-kappa B. Further, nuclear import of NF-kappa B activated apoptotic pathway in the cells that were blocked in mitosis by TN16 treatment suggesting that NF-kappa B acts as a pro-apoptotic protein in response to the suppression of microtubule dynamics. ...
Aspirin inhibits the activation of NF-kappa B, thus prevents the degradation of the NF-kappa B inhibitor, I kappa B, and therefore NF-kappa B is retained in the cytosol. Aspirin also inhibits NF-kappa B-dependent transcription from the Ig kappa enhancer and the human immunodeficiency virus (HIV) long terminal repeat (LTR) in transfected T cells. [1] Aspirin and salicylate are mediated in part by their specific inhibition of IKK-beta, thereby preventing activation by NF-kappaB of genes involved in the pathogenesis of the inflammatory response. [2] Aspirin is protective against neurotoxicity elicited by the excitatory amino acid glutamate in rat primary neuronal cultures and hippocampal slices. [3] Aspirin triggers transcellular biosynthesis of a previously unrecognized class of eicosanoidsduring coincubations of human umbilical vein endothelial cells (HUVEC) and neutrophils [polymorphonuclear leukocytes (PMN)]. Aspirin evokes a unique class of eicosanoids formed by acetylated PGHS-2 and ...
Early life adversity increases the risk for later infection. The febrile response is a potent mechanism to combat infection. We found that variations in maternal care influence the febrile response to 50µg/kg lipopolysaccharide (LPS) challenge in adult male rats. Offspring from low-licking/grooming (LG) mothers had an increased febrile response compared to offspring from high-LG mothers challenged with LPS. Low-LG offspring had reduced plasma IL-6 at one and two hours post challenge compared to high-LG offspring. IL-6 gene expression in the anterior hypothalamus was induced following LPS challenge in low-LG offspring but not in high-LG offspring at two hours post challenge. Occupancy of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) to the IL-6 promoter region in the anterior hypothalamus was greater in low-LG offspring treated with LPS than in high-LG offspring. These findings suggest greater activation of thermoregulatory neurons in the ...
I kappa B-alpha inhibits transcription factor NF-kappa B by retaining it in the cytoplasm. Various stimuli, typically those associated with stress or pathogens, rapidly inactivate I kappa B-alpha. This liberates NF-kappa B to translocate to the nucleus and initiate transcription of genes important for the defense of the organism. Activation of NF-kappa B correlates with phosphorylation of I kappa B-alpha and requires the proteolysis of this inhibitor. When either serine-32 or serine-36 of I kappa B-alpha was mutated, the protein did not undergo signal-induced phosphorylation or degradation, and NF-kappa B could not be activated. These results suggest that phosphorylation at one or both of these residues is critical for activation of NF-kappa B. ...
TY - JOUR. T1 - Various Mechanisms Involve the Nuclear Factor (Erythroid-Derived 2)-Like (NRF2) to Achieve Cytoprotection in Long-Term Cisplatin-Treated Urothelial Carcinoma Cell Lines. AU - Skowron, Margaretha A.. AU - Niegisch, Guenter. AU - Albrecht, Philipp. AU - van Koeveringe, Gommert. AU - Romano, Andrea. AU - Albers, Peter. AU - Schulz, Wolfgang A.. AU - Hoffmann, Michele J.. PY - 2017/8. Y1 - 2017/8. KW - urothelial carcinoma (UC). KW - cisplatin resistance. KW - nuclear factor (erythroid-derived 2)-like 2 (NRF2). KW - sequestosome 1 (p62. KW - SQSTM1). KW - Kelch-like ECH-associated protein 1 (KEAP1). KW - cytoprotection. KW - glutathione. KW - nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B) pathway. KW - hippo pathway. KW - OVARIAN-CANCER CELLS. KW - BLADDER-CANCER. KW - OXIDATIVE STRESS. KW - SIGNALING PATHWAY. KW - CHEMOTHERAPEUTIC-AGENTS. KW - TRANSCRIPTION FACTORS. KW - ANTIOXIDANT RESPONSE. KW - CROSS-TALK. KW - BETA-TRCP. KW - RESISTANCE. U2 - ...
Exposure of mammalian cells to radiation triggers the ultraviolet (UV) response, which includes activation of activator protein-1 (AP-1) and nuclear factor kappa B (NF-kappa B). This was postulated to occur by induction of a nuclear signaling cascade by damaged DNA. Recently, induction of AP-1 by UV was shown to be mediated by a pathway involving Src tyrosine kinases and the Ha-Ras small guanosine triphosphate-binding protein, proteins located at the plasma membrane. It is demonstrated here that the same pathway mediates induction of NF-kappa B by UV. Because inactive NF-kappa B is stored in the cytosol, analysis of its activation directly tests the involvement of a nuclear-initiated signaling cascade. Enucleated cells are fully responsive to UV both in NF-kappa B induction and in activation of another key signaling event. Therefore, the UV response does not require a signal generated in the nucleus and is likely to be initiated at or near the plasma membrane. ...
INTRODUCTION: To explore the effect of rosiglitazone on myocardial injury in septic rats through the nuclear factor kappa-light-chain-enhancer of
The NF-kappaB/Rel transcription factors participate in the activation of immune system regulatory genes and viral early genes including the human immunodeficiency virus type 1 long terminal repeat. NF-kappaB/Rel proteins are coupled to inhibitory molecules, collectively termed IkappaB, which are responsible for cytoplasmic retention of NF-kappaB. Cell activation leads to the phosphorylation and degradation of IkappaBalpha, permitting NG-kappaB/Rel translocation to the nucleus and target gene activation. To further characterize the signaling events that contribute to IkappaBalpha phosphorylation, a kinase activity was isolated from Jurkat T cells that specifically interacted with IkappaBalpha in an affinity chromatography step and phosphorylated IkappaBalpha with high specificity in vitro. By using an in-gel kinase assay with recombinant IkappaBalpha as substrate, two forms of the kinase (43 and 38 kDa) were identified. Biochemical criteria and immunological cross-reactivity identified the kinase ...
Metformin, an inexpensive and well-tolerated oral agent commonly used in the first-line treatment of type 2 diabetes, has become the focus of intense research as a candidate anticancer agent. Here, we discuss the potential of metformin in cancer therapeutics, particularly its functions in multiple signaling pathways, including AMP-activated protein kinase, mammalian target of rapamycin, insulin-like growth factor, c-Jun N-terminal kinase/mitogen-activated protein kinase (p38 MAPK), human epidermal growth factor receptor-2, and nuclear factor kappaB pathways. In addition, cutting-edge targeting of cancer stem cells by metformin is summarized.
Acute psychosocial stress stimulates transient increases in circulating pro-inflammatory plasma cytokines, but little is known about stress effects on anti-inflammatory cytokines or underlying mechanisms. We investigated the stress kinetics and interrelations of pro- and anti-inflammatory measures on the transcriptional and protein level.,br /,,br /,Forty-five healthy men were randomly assigned to either a stress or control group. While the stress group underwent an acute psychosocial stress task, the second group participated in a non-stress control condition. We repeatedly measured before and up to 120 min after stress DNA binding activity of the pro-inflammatory transcription factor NF-κB (NF-κB-BA) in peripheral blood mononuclear cells, whole-blood mRNA levels of NF-κB, its inhibitor IκBα, and of the pro-inflammatory cytokines interleukin (IL)-1ß and IL-6, and the anti-inflammatory cytokine IL-10. We also repeatedly measured plasma levels of IL-1ß, IL-6, and IL-10.,br /,,br /,Compared ...
Intracranial aneurysms are associated with disturbed velocity patterns, and chronic inflammation, but the relevance for these findings are currently unknown. Here, we show that (disturbed) shear stress induced by vortices is a sufficient condition to activate the endothelial NF-kB pathway, possibly through a mechanism of mechanosensor de-activation. We provide evidence for this statement through in-vitro live cell imaging of NF-kB in HUVECs exposed to different flow conditions, stochastic modelling of flow induced NF-kB activation and induction of disturbed flow in mouse carotid arteries. Finally, CFD and immunofluorescence on human intracranial aneurysms showed a correlation similar to the mouse vessels, suggesting that disturbed shear stress may lead to sustained NF-kB activation thereby offering an explanation for the close association between disturbed flow and intracranial aneurysms.
Results (1) PAH specimens showed co-localisation of p65 within CD68+ macrophages in 75.4 (64.8-84.6)% of samples. Airway epithelium, neutrophils and lymphocytes were also positive for p65. (2) Pulmonary arterial medial thickness was increased in PAH compared to controls, at 33.7 (18.8-67.9)% in vessels 100-250 mm external diameter (E.D.) and 27.2 (14.8-44.2)% in vessels 250-500 mm ED, vs 17.7 (11.2-30.3)% and 14.9 (11.8-17.8)% in controls (p,0.0001 between groups). (3) Nuclear p65 was present in pulmonary artery endothelial cells (EC) but not other vascular cells including pulmonary artery smooth muscle cells in PAH: 53.9 (0-100)% of vessels 100-250 mm E.D. and 53.1 (0-100)% of those 250-500 mm E.D. scored EC p65 positivity in PAH compared to 7.5 (0-25.0)% in 100-250 mm ED and 4.7 (0-21.1)% in 250-500 mm ED in controls (p,0.0001 between groups) (Abstract P29 Figure 1). ...
Specific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors identified as homologs of Toll in Drosophila. Mammalian TLRs are expressed on innate immune cells, such as macrophages and dendritic cells, and respond to the membrane components of Gram-positive or Gram-negative bacteria. Pathogen recognition by TLRs provokes rapid activation of innate immunity by inducing production of proinflammatory cytokines and upregulation of costimulatory molecules. TLR signaling pathways are separated into two groups: a MyD88-dependent pathway that leads to the production of proinflammatory cytokines with quick activation of NF-{kappa}B and MAPK, and a MyD88-independent pathway associated with the induction of IFN-beta and IFN-inducible genes, and maturation of dendritic cells with slow activation of NF-{kappa}B and MAPK ...
Chemotherapy resistance of pancreatic cancer has been previously associated with hyperactivity of NF-κB [7, 11, 19, 33]. The discovery that GSK-3 regulates NF-κB [26], and that its inhibition has anti-inflammatory and growth inhibitory effects, holds promise to resolve the problem of drug resistance in cancers with inflammatory origin including pancreatic cancer [26, 28, 34]. In this paper, using a panel of six genetically distinct pancreatic cancer cell lines we confirmed previous reports that pharmacological inhibition of GSK-3 suppresses NF-κB transcriptional activity and is toxic to pancreatic cancer cells in a dose- and time-dependent manner [28]. We also show for the first time that GSK-3 inhibition potently reduces the clonogenic survival of pancreatic cancer cells. However, contrary to our hypothesis GSK-3/NF-κB inhibition did not sensitize to gemcitabine chemotherapy.. GSK-3 is a kinase involved in many cellular processes including energy metabolism, transcriptional regulation, cell ...
Vaccinia virus (VACV) protein N1 is an intracellular virulence factor and belongs to a family of VACV B-cell lymphoma (Bcl)-2-like proteins whose members inhibit apoptosis or activation of pro-inflammatory transcription factors, such as interferon (I
In vivo IkappaB alpha is a stronger inhibitor of NF-kappaB than is IkappaB beta. This difference is directly correlated with their varying abilities to inhibit NF-kappaB binding to DNA in vitro and in vivo. Moreover, IkappaB alpha, but not IkappaB beta, can remove NF-kappaB from functional preinitiation complexes in in vitro transcription experiments. Both IkappaBs function in vivo not only in the cytoplasm but also in the nucleus, where they inhibit NF-kappaB binding to DNA. The inhibitory activity of IkappaB beta, but not that of IkappaB alpha, is facilitated by phosphorylation of the C-terminal PEST sequence by casein kinase II and/or by the interaction of NF-kappaB with high-mobility group protein I (HMG I) on selected promoters. The unphosphorylated form of IkappaB beta forms stable ternary complexes with NF-kappaB on the DNA either in vitro or in vivo. These experiments suggest that IkappaB alpha works as a postinduction repressor of NF-kappaB independently of HMG I, whereas IkappaB beta ...
Background Nuclear factor kappa B (NF-B) is certainly a key nuclear transcription factor that controls the transcription of varied genes; and its own activation is certainly tightly managed by Inhibitor kappa B kinase (IKK). the data source size. Subsequently, recursive partitioning (RP) and docking filter systems were utilized to display screen the pharmacophore strikes. Finally, 29 substances were chosen for IKK enzyme inhibition assay to recognize a novel little molecule inhibitor of IKK em /em proteins. Conclusions In todays investigation, weve applied different computational versions sequentially to practically display screen the ChemDiv data source, and identified a little molecule which has an IC50 worth of 20.3 em /em M. This substance is certainly book among the known IKK em /em inhibitors. Further marketing from the strike substance can reveal a far more powerful anti-inflammatory agent. History Inhibitor kappa-B kinase em /em (IKK em /em ) is certainly a serine-threonine proteins ...
Prostate cancer (PCa) is the most frequently diagnosed cancer and the second most common cause of cancer deaths in men in the UK, despite the progress that has been made in PCa treatment. Nuclear Factor kappa B (NF-κB) regulates several genes involved in immune response, inflammation,proliferation and apoptosis. Overexpression of NF-κB has been shown to be involved in tumour progression and radiation therapy resistance of PCa. One potential approach in PCa cancer treatment therefore involves targeting IκBkinases (IKKs) which are key regulators of the NF-κB signaling pathway. Whilst IKKβ regulates the canonical NF-κB pathway involving degradation of IκB-α and phosphorylation of p65, IKKα regulates the non-canonical NF-κB pathway by mediating the processing of p100 to p52. Inhibition of NF-κB signaling by targeting IKKβ is a sub-optimal treatment choice as it has been shown to be associated with multiple serious toxicities. However, IKKα is of interest in PCa therapy as it has been ...
Background: Pulpitis is a complicated chronic inflammatory process which in a dynamic balance between damage and repair. Extracellular matrix plays an important regulatory role in wound healing and tissue repair. The aim of this study was to explore role of the epigenetic mark, enhancer of zes...
Inflammation is a beneficial mechanism that is usually triggered by injury or infection and is designed to return the body to homeostasis. However, uncontrolled or sustained inflammation can be deleterious and has been shown to be involved in the etiology of several diseases, including inflammatory bowel disorder and asthma. Therefore, effective anti-inflammatory signaling is important in the maintenance of homeostasis in the body. However, the inter-play between pro- and anti-inflammatory signaling is not fully understood. In the present study, we develop a mathematical model to describe integrated pro- and anti-inflammatory signaling in macrophages. The model incorporates the feedback effects of de novo synthesized pro-inflammatory (tumor necrosis factor alpha; TNF-a) and anti-inflammatory (interleukin-10; IL-10) cytokines on the activation of the transcription factor nuclear factor kappaB (NF-kB) under continuous lipopolysaccharide (LPS) stimulation (mimicking bacterial infection). In the ...
To investigate whether glutamine supplementation modulates intestinal nuclear factor kappa B (NF-kappaB) activity and pro-inflammatory cytokine expression after
Human pTECs are not only passive bystanders in the development of diabetic nephropathy, but they also respond actively to hyperglycemia and AGEs by inducing NF-κB activation and NF-κB-dependent gene expression in vitro and in vivo. One defined AGE generated by lipoxidation and glycoxidation in diabetic nephropathy is CML (44,52,61,70,114). The presence of CML-modified proteins in the urine of type 2 diabetic patients and the in vitro observation that CML is a potent inducer of sustained NF-κB activation in pTECs suggest that CML might play a role in the development of diabetes renal complications. In addition, the observation that type 2 diabetic patients demonstrated excretion of tubular cells that was positive for activated NF-κBp65 and IL-6 antigen implies that the AGE/CML-RAGE-mediated NF-κB activation is functionally significant.. Indirect evidence for the role of NF-κB activation in diabetic nephropathy has already been given from clinical studies in which an increase in oxidative ...
Vascular disrupting agents (VDAs) represent a novel approach to the treatment of cancer, resulting in the collapse of tumor vasculature and tumor death. 5,6-dimethylxanthenone-4-acetic acid (DMXAA) is a VDA currently in advanced phase II clinical trials, yet its precise mechanism of action is unknown despite extensive preclinical and clinical investigations. Our data demonstrate that DMXAA is a novel and specific activator of the TANK-binding kinase 1 (TBK1)-interferon (IFN) regulatory factor 3 (IRF-3) signaling pathway. DMXAA treatment of primary mouse macrophages resulted in robust IRF-3 activation and ∼750-fold increase in IFN-β mRNA, and in contrast to the potent Toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS), signaling was independent of mitogen-activated protein kinase (MAPK) activation and elicited minimal nuclear factor κB-dependent gene expression. DMXAA-induced signaling was critically dependent on the IRF-3 kinase, TBK1, and IRF-3 but was myeloid differentiation ...
Our experiment showed that LIN28B was upregulated by inflammatory factor IKKβ and together with TCF7L2 sustained the stemness of cancer cells. Marotta and colleagues have demonstrated previously that the inflammatory transcription factor STAT3 was highly activated in the CD44+CD24− population (40). Recent reports analogously indicated that STAT3 phosphorylation was positively correlated with ALDH1 expression in cancer cell lines and human breast cancer samples (41). However, this study demonstrated a novel mechanism, indicating that activation of IKKβ, an inflammatory kinase in the NF-κB pathway, was strongly correlated with the expression of stemness genes, especially LIN28B in human breast cancer cell lines or tissues. Previous studies also showed that LIN28B promoted tumor cell transformation (23, 24) and had a functional role in the maintenance of CSCs (25, 26). Consistent with these findings, our experiment results showed that expression of LIN28B was highly positively correlated with ...
Introduction: We have previously reported that bacterial toxins, especially endotoxins such as lipopolysaccharides (LPS), might be important causative agents in the pathogenesis of rheumatoid arthritis (RA) in an in vitro model that simulates the potential effects of residing in damp buildings. Since numerous inflammatory processes are linked with the nuclear factor-kappa B (NF-kappa B), we investigated in detail the effects of LPS on the NF-kappa B pathway and the postulated formation of procollagen-endotoxin complexes. Methods: An in vitro model of human chondrocytes was used to investigate LPS-mediated inflammatory signaling. Results: Immunoelectron microscopy revealed that LPS physically interact with collagen type II in the extracellular matrix (ECM) and anti-collagen type II significantly reduced this interaction. BMS-345541 (a specific inhibitor of I kappa B kinase (IKK)) or wortmannin (a specific inhibitor of phosphatidylinositol 3-kinase (PI-3K)) inhibited the LPS-induced degradation of ...
Is predicted to contribute to IkappaB kinase activity. Involved in several processes, including epiboly involved in gastrulation with mouth forming second; negative regulation of I-kappaB kinase/NF-kappaB signaling; and somite specification. Predicted to localize to IkappaB kinase complex. Is expressed in several structures, including immature eye; nervous system; notochord; pectoral fin; and segmental plate. Human ortholog(s) of this gene implicated in fetal encasement syndrome and prostate cancer. Orthologous to human CHUK (component of inhibitor of nuclear factor kappa B kinase complex ...
Apoptosis induced by TNF-receptor I (TNFR1) is thought to proceed via recruitment of the adaptor FADD and caspase-8 to the receptor complex. TNFR1 signaling is also known to activate the transcription factor NF-kappa B and promote survival. The mechanism by which this decision between cell death and survival is arbitrated is not clear. We report that TNFR1-induced apoptosis involves two sequential signaling complexes. The initial plasma membrane bound complex (complex I) consists of TNFR1, the adaptor TRADD, the kinase RIP1, and TRAF2 and rapidly signals activation of NF-kappa B. In a second step, TRADD and RIP1 associate with FADD and caspase-8, forming a cytoplasmic complex (complex II). When NF-kappa B is activated by complex I, complex II harbors the caspase-8 inhibitor FLIP(L) and the cell survives. Thus, TNFR1-mediated-signal transduction includes a checkpoint, resulting in cell death (via complex II) in instances where the initial signal (via complex I, NF-kappa B) fails to be activated.
Antibodies for proteins involved in regulation of I-kappaB kinase/NF-kappaB signaling pathways, according to their Panther/Gene Ontology Classification
Pancreatic cancer is a major unsolved health problem because of its biological aggressiveness. In the last decade, traditional clinical cancer therapy regimens as surgical tumor resection, cytotoxic chemotherapy, and radiation therapy have been supplemented with individualized targeted therapies directed against molecular determinants of the tumor. In spite of improved multimodal therapeutic regimens, 5 year survival does not exceed 5 percent. Inherent or acquired resistance towards cytotoxic agents, ionizing radiation, or both, is one of the hallmarks of biological aggressiveness of pancreas cancer as a solid tumor. To develop a new chemotherapeutic agent is still a clinical major concern as well as the better understanding of etiopathogenesis and molecular biology of pancreatic cancer.. NF-kB is ubiquitous and can be detected in the cytoplasm of many cell types. Several researches have indicated that constitutive NF-kB activation may conduce to pancreatic tumorigenesis [15, 16]. Hence, the ...
Results: We observed no significant differences in tumour necrosis factor-alpha serum levels between the study groups. In the patient group, an increase in the tumour necrosis factor-alpha serum levels in patients carrying the tumour necrosis factor-alpha (-308 G/A) A allele compared to those without the A allele was found to be statistically significant. Additionally, an increase in the tumour necrosis factor-alpha serum levels in patients carrying tumour necrosis factor-alpha (-308 G/A) AA genotype compared with patients carrying the AG or GG genotypes was statistically significant. No significant differences were found in these 2 polymorphisms between the patient and control groups (p,0.05 ...
Abstract. The transcription factor NF kappa B (NF-κB) mediates the expression of numerous genes involved in diverse functions such as inflammation, immune respo
COPD is associated with chronic inflammation predominantly affecting the lung parenchyma and peripheral airways, resulting in largely irreversible and progressive airflow limitation. This inflammation is characterized by increased levels of alveolar macrophages, neutrophils and T lymphocytes, which are recruited from the circulation. Oxidative stress is important in driving this inflammation (1). NF-κB is known to be critical in the regulation of proinflammatory molecules during cellular responses, particularly TNF-α, IL-6 and IL-8. When phosphorylated, IκB dissociates from the NF-κB-IκB complex, resulting in the translocation of NF-κB from the cytoplasm to the nucleus. Activation of NF-κB is regarded as an important initial event in the airway inflammatory response to a variety of stimuli, including infectious agents, toxins, cytokines, growth factors and oxidant stress (1,5,18). NF-κB may represent a link between inflammation and oxidative stress in chronic inflammatory diseases (19). ...
The small molecule inhibitor of the proteasome, bortezomib, promotes apoptosis;this effect appears to be due in part to prevention of NF-kB activation, but the...
1. Chen, Z., Luo, H. Y., Steinberg, M. H., and Chui, D. H. BCL11A represses HBG transcription in K562 cells. Blood Cells Mol Dis, 42: 144-149, 2009. 2. Konishi, E., Tabuchi, Y., and Yamanaka, A. A simple assay system for infection-enhancing and -neutralizing antibodies to dengue type 2 virus using layers of semi-adherent K562 cells. J Virol Methods, 163: 360-367. 3. Navarro, F., Gutman, D., Meire, E., Caceres, M., Rigoutsos, I., Bentwich, Z., and Lieberman, J. miR-34a contributes to megakaryocytic differentiation of K562 cells independently of p53. Blood, 114: 2181-2192, 2009. 4. Reuter, S., Charlet, J., Juncker, T., Teiten, M. H., Dicato, M., and Diederich, M. Effect of curcumin on nuclear factor kappaB signaling pathways in human chronic myelogenous K562 leukemia cells. Ann N Y Acad Sci, 1171: 436-447, 2009. 5. Salvatori, F., Cantale, V., Breveglieri, G., Zuccato, C., Finotti, A., Bianchi, N., Borgatti, M., Feriotto, G., Destro, F., Canella, A., Breda, L., Rivella, S., and Gambari, R. ...
Activator of Chk1/Cdc25C pathway; Inhibitor of the transforming growth factor beta-activated kinase-1-mediated NF-kappaB activation pathway; Antidiabetic
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Complete information for NFRKB gene (Protein Coding), Nuclear Factor Related To KappaB Binding Protein, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
This proposal describes the 5-year training program for the development of an academic career in molecular biology and Neonatology. The candidate is in his fina...
An increased level of the cytokine tumor necrosis factor alpha (TNFα) has been shown to be involved in the manifestation of both chronic pain and depression with respect to the hippocampus. Previous studies in this lab ...
NF-kappa-B essential modulator (NEMO) also known as inhibitor of nuclear factor kappa-B kinase subunit gamma (IKK-γ) is a ... Li X, Commane M, Nie H, Hua X, Chatterjee-Kishore M, Wald D, Haag M, Stark GR (September 2000). "Act1, an NF-kappa B-activating ... Li X, Commane M, Nie H, Hua X, Chatterjee-Kishore M, Wald D, Haag M, Stark GR (September 2000). "Act1, an NF-kappa B-activating ... Shifera AS, Horwitz MS (March 2008). "Mutations in the zinc finger domain of IKK gamma block the activation of NF-kappa B and ...
Li X, Commane M, Nie H, Hua X, Chatterjee-Kishore M, Wald D, Haag M, Stark GR (Oct 2000). "Act1, an NF-kappa B-activating ... Qian Y, Zhao Z, Jiang Z, Li X (2002). "Role of NF kappa B activator Act1 in CD40-mediated signaling in epithelial cells". Proc ... 2002). "Association of the adaptor TANK with the I kappa B kinase (IKK) regulator NEMO connects IKK complexes with IKK epsilon ... This gene encodes a protein involved in regulating responses to cytokines by members of the Rel/NF-kappaB transcription factor ...
"FLASH coordinates NF-kappa B activity via TRAF2". J. Biol. Chem. 276 (27): 25073-7. doi:10.1074/jbc.M102941200. PMID 11340079. ... "FLASH coordinates NF-kappa B activity via TRAF2". J. Biol. Chem. 276 (27): 25073-7. doi:10.1074/jbc.M102941200. PMID 11340079. ... "Role of FLASH in caspase-8-mediated activation of NF-kappaB: dominant-negative function of FLASH mutant in NF-kappaB signaling ...
"FLASH coordinates NF-kappa B activity via TRAF2". J. Biol. Chem. 276 (27): 25073-7. doi:10.1074/jbc.M102941200. PMID 11340079. ... "Critical roles of TRAF2 and TRAF5 in tumor necrosis factor-induced NF-kappa B activation and protection from cell death". J. ... "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97-105. ... activates NF-kappaB and stress-activated protein kinase/c-Jun N-terminal kinase via TRAF2, TRAF5, and NF-kappaB-inducing kinase ...
CARDs induce nuclear factor kappa-B (NF-κB; MIM 164011) activity through the IKK (e.g., IKBKB; MIM 603258) complex. CARD9 (MIM ... caspase recruitment domain/membrane-associated guanylate kinase family member that interacts with BCL10 and activates NF-kappa ... caspase recruitment domain/membrane-associated guanylate kinase family member that interacts with BCL10 and activates NF-kappa ... a MAGUK family member linking protein kinase C activation to Bcl10-mediated NF-kappaB induction". J. Biol. Chem. 276 (33): ...
NFKBIZ: NF-kappa-B inhibitor zeta. *PARP14 encoding protein Poly(ADP-ribose) polymerase family member 14 ...
Sivasubramanian N, Adhikary G, Sil PC, Sen S (1996). "Cardiac myotrophin exhibits rel/NF-kappa B interacting activity in vitro ... 2002). "Myotrophin/V-1, a protein up-regulated in the failing human heart and in postnatal cerebellum, converts NFkappa B p50- ... converts NFkappa B p50-p65 heterodimers to p50-p50 and p65-p65 homodimers". J. Biol. Chem. United States. 277 (26): 23888-97. ...
PDB: 1SVC​;Müller CW, Rey FA, Sodeoka M, Verdine GL, Harrison SC (January 1995). "Structure of the NF-kappa B p50 homodimer ... The Rel homology domain (RHD) is a protein domain found in a family of eukaryotic transcription factors, which includes NF-κB, ... element-specific transcriptional activity of differentially phosphorylated nuclear factor-kappa B". J. Biol. Chem. 280 (1): 244 ...
Verstrepen L, Carpentier I, Verhelst K, Beyaert R (July 2009). "ABINs: A20 binding inhibitors of NF-kappa B and apoptosis ... "Expression of the NF-kappaB inhibitor ABIN-3 in response to TNF and toll-like receptor 4 stimulation is itself regulated by NF- ... "LIND/ABIN-3 is a novel lipopolysaccharide-inducible inhibitor of NF-kappaB activation". J. Biol. Chem. 282 (1): 81-90. doi: ...
Akt and calcineurin are both activators of NF kappa B (p65). Through their activation PGC-1α seems to activate NF kappa B. ... Other groups found that PGC-1s inhibit NF kappa B activity. The effect was demonstrated for PGC-1 alpha and beta. PGC-1α has ... Increased activity of NF kappa B in muscle has recently been demonstrated following induction of PGC-1α. The finding seems to ... Viatour P, Merville MP, Bours V, Chariot A (January 2005). "Phosphorylation of NF-kappaB and IkappaB proteins: implications in ...
"CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-kappa B activation". Nat. Immunol. 3 (9): 836-43. doi: ... family members that interact with BCL10 and activate NF-kappa B". J. Biol. Chem. 276 (15): 11877-82. doi:10.1074/jbc.M010512200 ... family members that interact with BCL10 and activate NF-kappa B". J. Biol. Chem. 276 (15): 11877-82. doi:10.1074/jbc.M010512200 ... "A requirement for CARMA1 in TCR-induced NF-kappa B activation". Nat. Immunol. 3 (9): 830-5. doi:10.1038/ni824. PMID 12154356. ...
and its expression is completely dependent on NF- kappa B signaling pathway. Aire recognizes target genes of TRAs via specific ... Similarly to Aire expression, mTECs development is highly dependent on NF- kappa B signaling pathway. Linsk R, Gottesman M, ... Gordon J, Wilson VA, Blair NF, Sheridan J, Farley A, Wilson L, Manley NR, Blackburn CC (May 2004). "Functional evidence for a ... Ulyanchenko S, O'Neill KE, Medley T, Farley AM, Vaidya HJ, Cook AM, Blair NF, Blackburn CC (March 2016). "Identification of a ...
Scheinman RI, Beg AA, Baldwin AS (Oct 1993). "NF-kappa B p100 (Lyt-10) is a component of H2TF1 and can function as an I kappa B ... Baldwin AS (1996). "The NF-kappa B and I kappa B proteins: new discoveries and insights". Annual Review of Immunology. 14: 649- ... "DNA binding and I kappa B inhibition of the cloned p65 subunit of NF-kappa B, a rel-related polypeptide". Cell. 64 (5): 961-9. ... newly synthesized I kappa B beta in persistent activation of NF-kappa B". Molecular and Cellular Biology. 16 (10): 5444-9. doi: ...
Baeuerle, P.A. (1991). "The inducible transcription activator NF-kappa B: regulation by distinct protein subunits". Biochimica ... release IFN-alpha which acts on an autocrine and paracrine loop that up-regulates the levels of physiologically active NF-kappa ...
... monomethylates the RelA subunit of nuclear factor kappa B (NF-κB). RelA mono-methylation at lysine 310 (RelAK310me1) ... of the NF-κB subunit RelA by SETD6 couples activity of the histone methyltransferase GLP at chromatin to tonic repression of NF ... "Structural basis of SETD6-mediated regulation of the NF-kB network via methyl-lysine signaling". Nucleic Acids Research. 39 (15 ...
"Regulation of interleukin 12 p40 expression through an NF-kappa B half-site". Mol. Cell. Biol. 15 (10): 5258-67. doi:10.1128/ ...
Nuclear factor kappa-B (NF-κB), a signaling molecule, stimulates the inflammatory pathways. NF-κB inhibitor (IκB) downregulates ... When patients take rosiglitazone, NF-κB levels fall and IκB levels increase. Rosiglitazone was approved by the US FDA in 1999 ...
"Complex formation and cooperation of protein kinase C theta and Akt1/protein kinase B alpha in the NF-kappa B transactivation ... "Akt-dependent phosphorylation specifically regulates Cot induction of NF-kappa B-dependent transcription". Mol. Cell. Biol. 22 ... Ozes ON, Mayo LD, Gustin JA, Pfeffer SR, Pfeffer LM, Donner DB (Sep 1999). "NF-kappaB activation by tumour necrosis factor ... Romashkova JA, Makarov SS (Sep 1999). "NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling". Nature. 401 (6748): 86- ...
... a PYRIN-containing Apaf1-like protein that assembles with ASC and regulates activation of NF-kappa B". J. Biol. Chem. 277 (13 ... "ASC is an activating adaptor for NF-kappa B and caspase-8-dependent apoptosis". Biochem. Biophys. Res. Commun. 303 (1): 69-73. ... a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing ... "The PAAD/PYRIN-only protein POP1/ASC2 is a modulator of ASC-mediated nuclear-factor-kappa B and pro-caspase-1 regulation". ...
Rustgi AK, Van 't Veer LJ, Bernards R (November 1990). "Two genes encode factors with NF-kappa B- and H2TF1-like DNA-binding ... These proteins bind specific DNA sequences, including the kappa-B motif (GGGACTTTCC), in the promoters and enhancer regions of ...
Urban MB, Schreck R, Baeuerle PA (1991). "NF-kappa B contacts DNA by a heterodimer of the p50 and p65 subunit". EMBO J. 10 (7 ... Nuclear factor related to kappa-B-binding protein is a protein that in humans is encoded by the NFRKB gene. GRCh38: Ensembl ... Adams BS, Leung KY, Hanley EW, Nabel GJ (1992). "Cloning of R kappa B, a novel DNA-binding protein that recognizes the ... "Localization of the gene encoding R kappa B (NFRKB), a tissue-specific DNA binding protein, to chromosome 11q24-q25" (PDF). ...
Verma IM, Stevenson JK, Schwarz EM, Van Antwerp D, Miyamoto S (1995). "Rel/NF-kappa B/I kappa B family: intimate tales of ... "Control of NF-kappa B transcriptional activation by signal induced proteolysis of I kappa B alpha". Philos. Trans. R. Soc. Lond ... Prigent M, Barlat I, Langen H, Dargemont C (November 2000). "IkappaBalpha and IkappaBalpha /NF-kappa B complexes are retained ... IκBα inhibits NF-κB by masking the nuclear localization signals (NLS) of NF-κB proteins and keeping them sequestered in an ...
"A novel mitogen-inducible gene product related to p50/p105-NF-kappa B participates in transactivation through a kappa B site". ... Taylor JP, Pomerantz RJ, Oakes JW, Khalili K, Amini S (January 1995). "A CNS-enriched factor that binds to NF-kappa B and is ... Liu J, Perkins ND, Schmid RM, Nabel GJ (June 1992). "Specific NF-kappa B subunits act in concert with Tat to stimulate human ... February 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell ...
"Peptide-induced negative selection of thymocytes activates transcription of an NF-kappa B inhibitor". Mol. Cell. 9 (3): 637-48 ... After NF-κB activation atypical IκBs are induced by the transcription factor Atypical IκBs, in turn, can regulate the NF-κB ... IκBNS is a member of the atypical inhibitors of NF-κB (also called the nuclear IκBs). NF-κB is a transcription factor, which ... Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, delta also known as IκBNS is a protein in humans ...
Rustgi AK, Van 't Veer LJ, Bernards R (Nov 1990). "Two genes encode factors with NF-kappa B- and H2TF1-like DNA-binding ... Bettelli E, Dastrange M, Oukka M (Apr 2005). "Foxp3 interacts with nuclear factor of activated T cells and NF-kappa B to ... These proteins bind specific DNA sequences, including the kappa-B motif (GGGACTTTCC), in the promoters and enhancer regions of ...
"A mechanism of suppression of TGF-beta/SMAD signaling by NF-kappa B/RelA". Genes Dev. 14 (2): 187-97. doi:10.1101/gad.14.2.187 ... The interaction blocks the formation of the IRAK1-mediated IL-1R/TLR signaling complex therefore abrogates NF-κB activity, ...
"SHARPIN forms a linear ubiquitin ligase complex regulating NF-kappa B activity and apoptosis". Nature. 471 (7340): 637-641. ... pathogen Salmonella Typhimurium as the local NF-κB signalling platform and provided insights into the function of OTULIN in NF- ... RIPK1 and NF-kappaB signaling in Smac mimetic-induced cell death in breast cancer cells". Biol Chem. 400 (2): 171-180. doi: ... "Specific recognition of linear ubiquitin chains by NEMO is important for NF-κB activation". Cell. 136 (6): 1098-1109. doi: ...
1992). "A novel complex between the p65 subunit of NF-kappa B and c-Rel binds to a DNA element involved in the phorbol ester ... Kochel T, Rice NR (1992). "v-rel- and c-rel-protein complexes bind to the NF-kappa B site in vitro". Oncogene. 7 (3): 567-72. ... Kunsch C, Ruben SM, Rosen CA (1992). "Selection of optimal kappa B/Rel DNA-binding motifs: interaction of both subunits of NF- ... Beg AA, Baldwin AS (1994). "Activation of multiple NF-kappa B/Rel DNA-binding complexes by tumor necrosis factor". Oncogene. 9 ...
"Stimulation of ionotropic glutamate receptors activates transcription factor NF-kappa B in primary neurons". Proc. Natl. Acad. ...
Known aliases of TMEM101 include Putative NF-Kappa-B-Activating Protein 130, FLJ23987, and MGC4251. TMEM101 is located on the ... The TMEM101 protein has been demonstrated to activate the NF-κB signaling pathway. High levels of expression of TMEM101 have ... TMEM101 cDNA transcripts have been demonstrated to activate the transcription of NF-κB controlled genes in human embryonic ... "Large-scale identification and characterization of human genes that activate NF-κB and MAPK signaling pathways". Oncogene. 22. ...
Azzolina A, Bongiovanni A, Lampiasi N (Dec 2003). "Substance P induces TNF-alpha and IL-6 production through NF kappa B in ... substance P activates p38 mitogen-activated protein kinase resulting in IL-6 expression independently from NF-kappa B". Journal ...
... high levels of calcium in mitochondria elevates activity of nuclear factor kappa B NF-κB and transcription of CACNA1c and ...
Karin M, Delhase M (February 2000). "The I kappa B kinase (IKK) and NF-kappa B: key elements of proinflammatory signalling". ... Accordingly, gene expression by degradation of transcription factors, such as p53, c-Jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, ... Due to its role in generating the activated form of NF-κB, an anti-apoptotic and pro-inflammatory regulator of cytokine ... The proteasomal activation of NF-κB by processing p105 into p50 via internal proteolysis is one major example.[69] Some ...
TRAF2 and TRAF5 can interact with this receptor, and mediate the signal transduction that leads to the activation of NF-kappaB ... TRAF-2 mediates CD30-induced nuclear factor kappa B activation". Proceedings of the National Academy of Sciences of the United ... and CD30-TRAF signaling complexes that inhibits TRAF2-mediated NF-kappaB activation". The Journal of Experimental Medicine. 185 ...
"A physical and functional map of the human TNF alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97-105. ... releasing NF-κB. NF-κB is a heterodimeric transcription factor that translocates to the nucleus and mediates the transcription ... Activation of NF-κB: TRADD recruits TRAF2 and RIP. TRAF2 in turn recruits the multicomponent protein kinase IKK, enabling the ... For instance, NF-κB enhances the transcription of C-FLIP, Bcl-2, and cIAP1 / cIAP2, inhibitory proteins that interfere with ...
Davis JN, Kucuk O, Djuric Z, Sarkar FH (June 2001). "Soy isoflavone supplementation in healthy men prevents NF-kappa B ...
"A physical and functional map of the human TNF alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97-105. ... liberando o NF-κB. O NF-κB é un factor de transcrición heterodimérico que se transloca ao núcleo celular e é mediadora na ... Activación de NF-κB: TRADD recruta TRAF2 e RIP. Á súa vez TRAF2 recruta a proteína quinase multicompoñentes IKK, que permite ... Por exemplo, o NF-κB potencia a transcrición de C-FLIP, Bcl-2, e cIAP1 / cIAP2, proteínas inhibidoras que interfiren coa ...
Animation showing the five motions possible with a four-circle kappa goniometer. The rotations about each of the four angles φ ... Cotton FA, Curtis NF, Harris CB, Johnson BF, Lippard SJ, Mague JT, et al. (September 1964). "Mononuclear and Polynuclear ... The most common type of goniometer is the "kappa goniometer", which offers three angles of rotation: the ω angle, which rotates ...
"The enzymatic and DNA binding activity of PARP-1 are not required for NF-kappa B coactivator function". The Journal of ...
Effect on nuclear factor kappa B Certain poloxamers such as P85 have been shown not only to be able to transport target genes ... Certain poloxamers, such as P85 and L61, have also been shown to stimulate transcription of NF kappaB genes, although the ... bar that P85 has been shown to induce phosphorylation of the inhibitory kappa. ...
"Control of NF-kappa B transcriptional activation by signal induced proteolysis of I kappa B alpha". Philos. Trans. R. Soc. Lond ... Desterro JM, Rodriguez MS, Hay RT (1998). "SUMO-1 modification of IkappaBalpha inhibits NF-kappaB activation". Mol. Cell. 2 (2 ...
kappa}B in Developmental and Plasticity-Associated Synaptogenesis , revista = J. Neurosci. , volume = 31 , issue = 14 , páxinas ... Ademais dos estímulos que activan o NF-κB noutros tecidos, no sistema nervioso o NF-κB pode ser activado por factores de ... NF-κB (editar) Revisión como estaba o 3 de xuño de 2017 ás 10:33 9 bytes engadidos , hai 3 anos ... Os estudos actuais suxiren que o NF-κB é importante para a aprendizaxe e a memoria en múltiples organismos como [[cangrexo]]s,, ...
positive regulation of I-kappaB kinase/NF-kappaB signaling. • positive regulation of release of cytochrome c from mitochondria ... Interferon kappa (IFN-ε/κ/τ/ζ, IFNK). *Interferon omega (IFN-ω, IFNW1) ...
2001). "Two novel IL-1 family members, IL-1 delta and IL-1 epsilon, function as an antagonist and agonist of NF-kappa B ... 2004). "Interleukin (IL)-1F6, IL-1F8, and IL-1F9 signal through IL-1Rrp2 and IL-1RAcP to activate the pathway leading to NF- ... positive regulation of I-kappaB kinase/NF-kappaB signaling. • positive regulation of T cell differentiation. • positive ...
... and both Fas and TNF-R1 trigger events that activate the transcription factor nucléar factor kappa B (NF-κB), which induces the ...
"Entrez Gene: RBPJ recombination signal binding protein for immunoglobulin kappa J region".. ... "Physical interaction between a novel domain of the receptor Notch and the transcription factor RBP-J kappa/Su(H)". Current ... "A protein binding to the J kappa recombination sequence of immunoglobulin genes contains a sequence related to the integrase ... recombination signal binding protein for immunoglobulin kappa J region. ...
... function as an antagonist and agonist of NF-kappa B activation through the orphan IL-1 receptor-related protein 2". Journal of ...
A molecule called nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is known to play a critical role in ... The researchers found that if NF-κB activity was blocked in elderly mice by bathing them in bleach solution, the animals' skin ... "Topical hypochlorite ameliorates NF-κB-mediated skin diseases in mice". The Journal of Clinical Investigation. 123 (12): 5361- ...
Much of the attention on production of proinflammatory cytokines has focused on the IKK-beta/NF-kappa-B pathway, a protein ...
... a molecule involved in a NF-kappa B-independent pathway". The Journal of Biological Chemistry. 275 (30): 22780-9. doi:10.1074/ ... negative regulation of I-kappaB kinase/NF-kappaB signaling. • autophagy. • cellular protein localization. • G2/M transition of ... regulation of I-kappaB kinase/NF-kappaB signaling. • signal transduction. • Golgi to plasma membrane protein transport. • ...
positive regulation of NF-kappaB transcription factor activity. • activation of JUN kinase activity. • positive regulation of ... Interferon kappa (IFN-ε/κ/τ/ζ, IFNK). *Interferon omega (IFN-ω, IFNW1) ...
2004). „A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. England. ... čime se oslobađa NF-κB. NF-κB je heterodimerni transkripcioni faktor koji se translocira u nukleus i posreduje transkripciju ... Aktivacija NF-κB: TRADD regrutuje TRAF2 i RIP. TRAF22 zatim regrutuje multikomponentni protein kinazu IKK, što omogućava serin- ... pozitivna regulacija I-kapaB kinaze/NF-kapaB kaskade. • celularna ekstravazacija. • regulacija osteoklast diferencijacije. • ...
The promoter region of the VCAM-1 gene contains functional tandem NF-κB (nuclear factor-kappa B) sites. The sustained ...
... and NF-kappa B family proteins". Molecular and Cellular Biology. 15 (3): 1786-96. doi:10.1128/mcb.15.3.1786. PMC 230403. PMID ... "Functional interaction between the DNA binding subunit trimerization domain of NF-Y and the high mobility group protein HMG-I( ...
302(英语:Kappa number). *306(英语:Vicat softening point). *428(英语:ISO 428) ...
... na ang pinakamahalaga ang NF-κB (NF kappa B) na taas-na-nireregula kapag ang mga selulang T ay naging aktibo.[101] Ang ibig ... "Hostile takeovers: viral appropriation of the NF-kB pathway". J Clin Invest. 107 (2): 143-151. doi:10.1172/JCI11918. PMC ...
... which otherwise stimulates the production of NF-κB. ... Interferon kappa (IFN-ε/κ/τ/ζ, IFNK). *Interferon omega (IFN-ω ...
"Thioredoxin regulates the DNA binding activity of NF-kappa B by reduction of a disulphide bond involving cysteine 62". Nucleic ... NF-κB - by reducing a disulfide bond in NF-κB, Trx1 promotes binding of this transcription factor to DNA.[26] ... of human thioredoxin in a mixed disulfide intermediate complex with its target peptide from the transcription factor NF kappa B ...
In addition, MDM2 has p53-independent transcription factor-like effects in nuclear factor-kappa beta (NFκB) activation. ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
NF-kappa-B-activating protein is a protein that in humans is encoded by the NKAP gene. GRCh38: Ensembl release 89: ... "Entrez Gene: NKAP NF-kappaB activating protein". Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial ... Chen D, Li Z, Yang Q, Zhang J, Zhai Z, Shu HB (Oct 2003). "Identification of a nuclear protein that promotes NF-kappaB ... Zhande R, Karsan A (2007). "Erythropoietin promotes survival of primary human endothelial cells through PI3K-dependent, NF- ...
NF-kappa-B/Dorsal (IPR000451)*Nuclear factor NF-kappa-B, p105 subunit (IPR030503) ...
NF-kappa-B p65delta3Imported. ,p>Information which has been imported from another database using automatic procedures.,/p> ,p>, ... tr,Q13313,Q13313_HUMAN NF-kappa-B p65delta3 (Fragment) OS=Homo sapiens OX=9606 PE=2 SV=1 ...
Viral protein involved in the activation of host NF-kappa-B. This protein is a pleiotropic transcription factor which is ... Several viruses have developed strategies to activate the NF-kappa-B pathway in order to promote viral replication and prevent ... activation by virus of host NF-kappaB transcription factor activity [ GO:0039652 ]. ...
The NF-kappa B family of transcription proteins represents multiple DNA binding, rel related polypeptides that contribute to ... In this study multiple NF-kappa B related polypeptides ranging from 85 to 45 kDa were examined for their capacity to interact ... These experiments emphasize the role of NF-kappa B dimerization as a distinct level of transcriptional control that may permit ... Heterodimerization and transcriptional activation in vitro by NF-kappa B proteins.. Cohen L1, Hiscott J. ...
The IKK NF-kappa B system: a treasure trove for drug development.. Karin M1, Yamamoto Y, Wang QM. ...
In the cytosol, when complexed to an inhibitory molecule, I kappa B, NF-kappa B is in an inactive form and cannot bind DNA. ... Activation of cells with appropriate stimuli results in the dissociation of NF-kappa B from I kappa B and its translocation to ... Modulation of transcription factor NF-kappa B binding activity by oxidation-reduction in vitro.. M B Toledano and W J Leonard ... We now demonstrate that NF-kappa B binding in vitro can be inhibited by agents that modify free sulfhydryls. Binding is ...
Also considered to be a mediator for TAX activation of NF-kappa-B. Could be implicated in NF-kappa-B-mediated protection from ... the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B ... linked polyubiquitination of IKBKG which perturbs NF-kappa-B activation during bacterial infection. UniProt ...
NFX1 Plays a Role in Human Papillomavirus Type 16 E6 Activation of NFκB Activity Mei Xu, Rachel A. Katzenellenbogen, Carla ... Herpes Simplex Virus 1 Ubiquitin-Specific Protease UL36 Abrogates NF-κB Activation in DNA Sensing Signal Pathway Ruijie Ye, ... Molluscum Contagiosum Virus Protein MC005 Inhibits NF-κB Activation by Targeting NEMO-Regulated IκB Kinase Activation Gareth ... Cooperation of the Ebola Virus Proteins VP40 and GP1,2 with BST2 To Activate NF-κB Independently of Virus-Like Particle ...
Curcumin (diferuloylmethane) inhibits receptor activator of NF-kappa B ligand-induced NF-kappa B activation in osteoclast ... Gene deletion studies have shown that receptor activator of NF-kappaB ligand (RANKL) is one of the critical mediators of ... Treatment of these cells with RANKL activated NF-kappaB, and preexposure of the cells to curcumin completely suppressed RANKL- ... Pharmacological Actions : Enzyme Inhibitors : CK(692) : AC(347), NF-kappaB Inhibitor : CK(3536) : AC(2098) ...
I kappa B-alpha mRNA and protein levels are quickly induced by the activated NF-kappa B. This resurgence of I kappa B-alpha ... Mutual regulation of the transcriptional activator NF-kappa B and its inhibitor, I kappa B-alpha.. K Brown, S Park, T Kanno, G ... We propose a model in which NF-kappa B and I kappa B-alpha mutually regulate each other in a cycle: saturating amounts of the ... Transfection studies reveal that the I kappa B-alpha mRNA and the encoded protein are potently induced by NF-kappa B and by ...
... Paulina Kleniewska,1 ... The aim of the present study was to assess whether BAY 11-7082, a nuclear factor-kappaB (NF-κB) inhibitor, influences the level ... control). ET-1 administration slightly downregulated gene expression of p65 of NF-κB but potently and in a dose-dependent way ... of reactive oxygen species (ROS), tumor necrosis factor alpha (TNF-α), and NF-κB related signaling pathways in the liver. The ...
NF-kappaB transcription factors and the signaling pathways that activate them play a critical role in cancer development, ... NF-kappa B as a target for cancer therapy Expert Opin Ther Targets. 2007 Feb;11(2):133-44. doi: 10.1517/14728222.11.2.133. ... NF-kappaB transcription factors and the signaling pathways that activate them play a critical role in cancer development, ... This article presents a critical review on the different types of inhibitors targeting the NF-kappaB pathway at several stages ...
... nuclear form of NF-kappa B p65. The activation of NF-kappa B could be blocked with the antioxidant pyrrolidine dithiocarbamate ... which are encoded by genes known to be controlled by NF-kappa B. Moreover, NF-kappa B activity was found to change dramatically ... Stimulation of ionotropic glutamate receptors activates transcription factor NF-kappa B in primary neurons Proc Natl Acad Sci U ... Here we report that brief treatments with kainate or high potassium strongly activated NF-kappa B in granule cells from rat ...
These activate NF kappa B and may affect a variety of other transcription factors and apoptosis related proteins. ... Buy NF kappa B Activators from Santa Cruz. ... NF kappa B Activators offered by Santa Cruz activate NF kappa B ... NF kappa B Activators. Santa Cruz Biotechnology now offers a broad range of NF kappa B Activators. NFκB is a transcription ... ChemCruz™ Chemical NF kappa B Inhibitors for functional analysis of cellular responses to NF kappa B ...
NF-κB signaling is regulated by SIRT6, which is recruited to NF-κB target gene promoters by physical interaction with the NF-κB ... Researchers are increasingly linking aging and inflammation, and they are focusing their attention on the NF-kappa B (NF-κB) ... NF-κB (p65) is normally present in the cytoplasm in an inactive state. Figure 7(a) shows that very low NF-κB (p65) cytoplasmic ... For NF-κB (p65) staining, cells were incubated with the primary antibodies (NF-κB antibody, 1 : 500 dilution) for 2 hours at 37 ...
O perfil de ativação do NF-B foi avaliado em biópsias de 47 pacientes com diagnóstico clínico e laboratorial de hanseníase, ... The role of nuclear factor kappa B (NF-kappa B) activation in the cutaneous expression of leprosy ... Papel da ativação do fator nuclear kappa B (NF-kappa B) na expressão cutânea da hanseníase ... Índice de ativação NF-B >1 foi considerado representativo de ativação. Trinta e seis por cento dos pacientes apresentaram NF-B ...
This review focuses on the role of HDAC 3 in (NF-kappa B-mediated) inflammation and NF-kappa B lysine acetylation. In addition ... The nuclear factor kappa B (NF-kappa B) pathway is an important regulator in the expression of numerous inflammatory genes, and ... Histone deacetylase 3 (HDAC 3) as emerging drug target in NF-kappa B-mediated inflammation. Leus, N. G. J., Zwinderman, M. R. H ... An important challenge in targeting the regulatory role of HDACs in the NF-kappa B pathway is the development of highly potent ...
In contrast, IL-2 exerts only minor effects on NF-kappa B p65 mRNA expression. IL-2 induction of NF-kappa B through the IL-2R ... IL-2-induced signal transduction involves the activation of nuclear NF-kappa B expression.. N Arima, W A Kuziel, T A Grdina and ... IL-2 activation of nuclear NF-kappa B expression is regulated in part at a post-translational level, involving the rapid ... Together, these findings suggest that NF-kappa B may play an important role as one intracellular second messenger relaying ...
It is demonstrated here that the same pathway mediates induction of NF-kappa B by UV. Because inactive NF-kappa B is stored in ... and nuclear factor kappa B (NF-kappa B). This was postulated to occur by induction of a nuclear signaling cascade by damaged ... Enucleated cells are fully responsive to UV both in NF-kappa B induction and in activation of another key signaling event. ... NF-kappa B activation by ultraviolet light not dependent on a nuclear signal ...
In addition, we inhibited NF-κB activity in these cells and analyzed the effects on myogenic differentiation. We show that ... However, after treatment of the cells with two different small-molecule NF-κB-inhibiting compounds, the IKK inhibitor curcumin ... Thus, here, we tested whether the ubiquitous transcription factor NF-κB, which regulates myogenic differentiation and is also a ... For this purpose, we analyzed NF-κB activity (classical pathway) in myoblasts with different differentiation potential, ...
Jr Selective activation of NF-kappa B subunits in human breast cancer: potential roles for NF-kappa B2/p52 and for Bcl-3. ... NF-kappa B genes have a major role in Inflammatory Breast Cancer. Florence Lerebours,. 1,2 Sophie Vacher,1,2 Catherine Andrieu, ... NF-kappa B activation in human breast cancer specimens and its role in cell proliferation and apoptosis. Proc Natl Acad Sci USA ... The 35 upregulated genes included NF-κB genes (NFKB1, RELA, IKBKG, NFKBIB, NFKB2, REL, CHUK) and NF-κB-regulated genes involved ...
... kappa]B/c-Jun/AP-1-dependent pathway.(Research, cyclooxygenase-2, nuclear factor, Report) by Environmental Health Perspectives ... kappa]B[alpha] [inhibitor of transcription factor NF[kappa]B-[alpha]), phosphorylated I[kappa]B[alpha] (P-I[kappa]B[alpha]), c- ... kappa]B (I[kappa]B) kinase [beta]; an upstream kinase responsible for nuclear factor [kappa]B (NF[kappa]B) activation] or ... of COX-2 and activation of AP-1 and NF[kappa]B, and show that both AP-1 and NF[kappa]B are required for Cr(VI)-induced COX-2 ...
Results Administration with LV-ShRNA-Panx1 markedly decreased the expression levels of TLR2/4/NF-κB pathway-related agents in ... On the contrary, administration of LV-Panx1-EGFP elevated the expressions of TLR2/4/NF-κB pathway-related agents, which ... Conclusion Pannexin-1 channels may contribute to inflammatory response and neurobehavioral dysfunction through the TLR2/TLR4/NF ... and western blotting were performed to explore the potential interactive mechanism between Pannexin-1 channels and TLR2/TLR4/NF ...
... kappa $B signaling. Here we present a systematic way to derive a minimal model from an up-to-dated and detailed NF-$\kappa $B ... kappa $B signaling. Simulating the detailed ODE model for NF-$\kappa $B signaling network with large sets of the parameter ... Abstract: D35.00012 : Understanding Dynamic Patterns of NF-$\kappa $B Signaling: Derivation and Analysis of a Minimal Model ... Understanding the pleiotropism of NF-$\kappa $B signal transduction is a challenge of clear medical importance and systems ...
In addition, NF-kappa B p65 (RelA), but not NF-kappa B p50 (NFKB1), binds specifically to the NF-kappa B site. When incubated ... overexpression of the NF-kappa B inhibitor molecule, I kappa B, abolished the RelA- and RelA/NF-IL-6-dependent synergistic ... Synergistic transcriptional activation of the IL-8 gene by NF-kappa B p65 (RelA) and NF-IL-6.. C Kunsch, R K Lang, C A Rosen ... Because adjacent binding sites for the inducible transcription factors NF-kappa B and NF-IL-6 are located within this region, ...
Nuclear factor-kappa B (NF-kappa B) is the generic name of a family of transcription factors that function as dimers and ... NF-kappa B signaling pathway - Homo sapiens (human) [ Pathway menu , Organism menu , Pathway entry , Download KGML , Show ... There are several pathways leading to NF-kappa B-activation. The canonical pathway is induced by tumour necrosis factor-alpha ( ... which allows the p50/p65 NF-kappa B dimer to enter the nucleus and activate gene transcription. Atypical pathways are IKK- ...
... on IL-1β-mediated NF-κB-activation were examined. Results IL-1β increased NF-κB luciferase activity (8-fold) and NF-κB ... Our data suggest the inhibitory effects of L-Arg on NF-κB activation are mediated in part by iNOS since SNP preserves and NNA ... Conclusion The inhibitory effects of L-Arg on IL-1β-mediated NF-κB-activation in Caco-2 cells involve L-Arg transport activity ... System y+ CAT1 siRNA decreased CAT1 expression, L-Arg transport activity and attenuated the inhibitory effects of L-Arg on NF- ...
  • Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. (rcsb.org)
  • Mutual regulation of the transcriptional activator NF-kappa B and its inhibitor, I kappa B-alpha. (pnas.org)
  • The aim of the present study was to assess whether BAY 11-7082, a nuclear factor-kappaB (NF- κ B) inhibitor, influences the level of reactive oxygen species (ROS), tumor necrosis factor alpha (TNF- α ), and NF- κ B related signaling pathways in the liver. (hindawi.com)
  • However, after treatment of the cells with two different small-molecule NF-κB-inhibiting compounds, the IKK inhibitor curcumin and the proteasome inhibitor lactacystin, we found that neither curcumin nor lactacystin promoted myogenic differentiation in either normal myoblasts or rhabdomyosarcoma cells. (biomedsearch.com)
  • In addition, overexpression of the NF-kappa B inhibitor molecule, I kappa B, abolished the RelA- and RelA/NF-IL-6-dependent synergistic activation. (jimmunol.org)
  • Here, we provide the first evidence that the in vivo mechanism of NF-kappa B activation is through the phosphorylation and subsequent loss of its inhibitor, I kappa B alpha. (asm.org)
  • Phosphorylation and degradation of the cytoplasmic inhibitor I kappa B alpha are crucial regulatory events in the activation of NF-kappa B DNA-binding activity. (asm.org)
  • Nuclear expression of NF-kappa B occurs after its induced dissociation from its cytoplasmic inhibitor I kappa B alpha. (sciencemag.org)
  • Transfection studies indicate that the I kappa B alpha gene is specifically induced by the 65-kilodalton transactivating subunit of NF-kappa B. Association of the newly synthesized I kappa B alpha with p65 restores intracellular inhibition of NF-kappa B DNA binding activity and prolongs the survival of this labile inhibitor. (sciencemag.org)
  • We have cloned an inhibitor of NF-kappa B, I kappa BNS, which is rapidly expressed upon TCR-triggered but not dexamethasone- or gamma irradiation-stimulated thymocyte death. (ucm.es)
  • To evaluate the therapeutic efficacy of SN50, nuclear factor kappa B inhibitor, in corneal penetrating injury model in rats. (arvojournals.org)
  • Association with inhibitor kappa B-interacting NKIRAS1 and NKIRAS2 prevent its phosphorylation rendering it more resistant to degradation, explaining its slower degradation. (sdsc.edu)
  • Interacts with inhibitor kappa B-interacting Ras-like NKIRAS1 and NKIRAS2 (PubMed:10657303, PubMed:12672800, PubMed:15024091). (sdsc.edu)
  • We investigated the changes in NF-κB activation and therapeutic impact of NF-κB blockade by the novel NF-κB inhibitor dehydroxymethyl derivative of epoxyquinomicin (DHMEQ) in CDDP-resistant bladder cancer cells. (biomedcentral.com)
  • This gene encodes the regulatory subunit of the inhibitor of kappaB kinase (IKK) complex, which activates NF-kappaB resulting in activation of genes involved in inflammation, immunity, cell survival, and other pathways. (nih.gov)
  • The protein encoded by this gene belongs to the NF-kappa-B inhibitor family, which inhibit NF-kappa-B by complexing with, and trapping it in the cytoplasm. (nih.gov)
  • Upon degradation of the inhibitor, NF-kappa-B moves to the nucleus and activates transcription of specific genes. (gentaur.se)
  • Nf kappa activation inhibitor meaning. (informe.com)
  • Inhibition of GADD45alpha and gamma in cancer cells by small interfering RNA abrogates apoptosis induction by the inhibitor of NF-kappaB and blocks c-Jun N-terminal kinase activation, whereas overexpression of GADD45alpha and gamma activates c-Jun N-terminal kinase and induces apoptosis. (scienceexchange.com)
  • Baeuerle PA, Baltimore D (1988) IKB: a specific inhibitor of the NF-κ 'B transcription factor. (springer.com)
  • FLICE inhibitory protein (FLIP) is an established inhibitor of caspase-8-mediated apoptosis, and it is also involved in NF-kappa B activation. (cdc.gov)
  • NF-kappa-B essential modulator (NEMO) also known as inhibitor of nuclear factor kappa-B kinase subunit gamma (IKK-γ) is a protein that in humans is encoded by the IKBKG gene. (wikipedia.org)
  • NEMO (IKK-γ) is the regulatory subunit of the inhibitor of IκB kinase (IKK) complex, which activates NF-κB resulting in activation of genes involved in inflammation, immunity, cell survival, and other pathways. (wikipedia.org)
  • Several viruses have developed strategies to activate the NF-kappa-B pathway in order to promote viral replication and prevent virus-induced apoptosis. (uniprot.org)
  • This article presents a critical review on the different types of inhibitors targeting the NF-kappaB pathway at several stages. (nih.gov)
  • The aim of the study was to investigate the effect of icariin (ICA) on cardiac aging through its effects on the SIRT6 enzyme and on the NF- κ B pathway. (hindawi.com)
  • The nuclear factor kappa B (NF-kappa B) pathway is an important regulator in the expression of numerous inflammatory genes, and acetylation plays a crucial role in regulating its responses. (rug.nl)
  • An important challenge in targeting the regulatory role of HDACs in the NF-kappa B pathway is the development of highly potent small molecules that selectively target HDAC iso-enzymes. (rug.nl)
  • It is demonstrated here that the same pathway mediates induction of NF-kappa B by UV. (sciencemag.org)
  • For this purpose, we analyzed NF-κB activity (classical pathway) in myoblasts with different differentiation potential, specifically in three different rhabdomyosarcoma cell lines. (biomedsearch.com)
  • The NF-κB pathway appears to play a major role in IBC, possibly contributing to the unusual phenotype and aggressiveness of this form of breast cancer. (pubmedcentralcanada.ca)
  • Hexavalent chromium Cr(VI) up-regulates COX-2 expression through an NF[kappa]B/c-Jun/AP-1-dependent pathway. (thefreelibrary.com)
  • CONCLUSION: We demonstrate for the first time that Cr(VI) is able to induce COX-2 expression via an NF[kappa]B/c-Jun/AP-1-dependent pathway. (thefreelibrary.com)
  • The Quantitative real-time polymerase chain reaction, electrophoretic mobility shift assay, enzyme-linked immunosorbent assay, immunofluorescence staining, and western blotting were performed to explore the potential interactive mechanism between Pannexin-1 channels and TLR2/TLR4/NF-κB-mediated signaling pathway. (frontiersin.org)
  • Administration with LV-ShRNA-Panx1 markedly decreased the expression levels of TLR2/4/NF-κB pathway-related agents in the brain cortex and significantly ameliorated neurological cognitive and memory deficits in this SAH model. (frontiersin.org)
  • On the contrary, administration of LV-Panx1-EGFP elevated the expressions of TLR2/4/NF-κB pathway-related agents, which correlated with augmented neuronal apoptosis. (frontiersin.org)
  • Pannexin-1 channels may contribute to inflammatory response and neurobehavioral dysfunction through the TLR2/TLR4/NF-κB-mediated pathway signaling after SAH, suggesting a potential role of Pannexin-1 channels could be a potential therapeutic target for the treatment of SAH. (frontiersin.org)
  • This pathway relies on IKK- mediated IkappaB-alpha phosphorylation on Ser32 and 36, leading to its degradation, which allows the p50/p65 NF-kappa B dimer to enter the nucleus and activate gene transcription. (kegg.jp)
  • The Zi Qi decoction also suppressed activation of the Toll-like receptor 4 (TLR4)-related NF-kappaB signaling pathway and subsequently inhibited the nuclear translocation of activated NF-kappaB. (medscimonit.com)
  • Together, these results show that NF-kappa B controls the expression of I kappa B alpha by means of an inducible autoregulatory pathway. (sciencemag.org)
  • Mullerian inhibiting substance inhibits breast cancer cell growth through an NFkappa B-mediated pathway. (harvard.edu)
  • Phosphorylation of serine residues on the I-kappa-B proteins by kinases (IKBKA, MIM 600664, or IKBKB, MIM 603258) marks them for destruction via the ubiquitination pathway, thereby allowing activation of the NFKB complex. (biomol.com)
  • Thiol agents and Bcl-2 identify an alphavirus-induced apoptotic pathway that requires activation of the transcription factor NF-kappa B. (rupress.org)
  • These results suggested that the inhibition was caused by oxidation of NF kappa B on a sensitive thiol, possibly on the p50 subunit (which was detected in NF kappa B complexes in both cell types), and not by inhibition of the activation pathway. (tcd.ie)
  • Hostile takeovers: viral appropriation of the NF- kappaB pathway. (lymerick.net)
  • For several reasons, the NF- kB pathway provides an attractive target to viral pathogens. (lymerick.net)
  • In this review, we will describe strategies that viruses have evolved to modulate the NF- kB pathway, to enhance viral replication, host cell survival, and evasion of immune responses. (lymerick.net)
  • It appears, however, that also several bacterial or parasitic intracellular infections activate NF- kB pathway like described above for the viral infections. (lymerick.net)
  • Zhan Q, Song R, Li F, Ao L, Zeng Q, Xu D, Fullerton DA, Meng X. Double-stranded RNA upregulates the expression of inflammatory mediators in human aortic valve cells through the TLR3-TRIF-noncanonical NF-?B pathway. (ucdenver.edu)
  • Phosphorylation of serine residues on these proteins by kinases marks them for destruction via the ubiquitination pathway, thereby allowing activation of the NF-kappa-B, which translocates to the nucleus to function as a transcription factor. (nih.gov)
  • our data establish the importance of a novel tumor suppressive IKBB gene in abrogating angiogenesis in NPC via the NF-kappaB signalling pathway. (nih.gov)
  • Dll1 quiescent tumor stem cells drive chemoresistance in breast cancer through NF -κB survival pathway. (wroc.pl)
  • Carvacrol protects neuroblastoma SH-SY5Y cells against Fe(2+)-induced apoptosis by suppressing activation of MAPK/JNK-NF-κB signaling pathway. (uni-bielefeld.de)
  • The NF-kappaB/IkappaB signaling pathway is a critical regulator of cell survival in cancer. (scienceexchange.com)
  • Gram-positive bacteria stimulate Toll-like receptor (TLR) 2 and then activate the pro-inflammatory nuclear factor-kappa B (NF-κB) pathway. (biomedcentral.com)
  • NF-κB pathway can be activated by the TLR2 ligand and inhibited by IκK inhibitors in the ocular surface cell culture system. (biomedcentral.com)
  • The regulation of NF-κB is highly context- and tissue-dependent, so it is important to define the triggers and targets of this pathway in healthy ocular surface and in disease. (biomedcentral.com)
  • Monitor the NF-kB signaling pathway. (abeomics.com)
  • Screen for activators or inhibitors of the NF-kB signaling pathway. (abeomics.com)
  • The present chapter discusses the role of NF-κB in cancer promotion and different drug targets, targeting NF-κB pathway for the treatment of cancers. (springer.com)
  • Rothwarf DM, Karin M (1999) The NF-κB activation pathway: a paradigm in information transfer from membrane to nucleus. (springer.com)
  • Tergaonkar V, Bottero V, Ikawa M, Li Q, Verma IM (2003) IκB kinase-independent IκBα degradation pathway: functional NF-κB activity and implications for cancer therapy. (springer.com)
  • Collectively, our study reveals a novel pathway for FLIP regulation of NF-kappa B through protein S-nitrosylation, which is a key posttranslational mechanism controlling DR-mediated cell death and survival. (cdc.gov)
  • Notably, the NBD peptide targets the inflammation induced NF-κB activation pathway sparing the protective functions of basal NF-κB activity allowing for greater therapeutic value and fewer undesired side effects. (wikipedia.org)
  • IL-2 induction of NF-kappa B through the IL-2R beta subunit was both correlated with activation of the endogenous IL-2R alpha gene and critically dependent upon the presence of a serine-rich cytoplasmic domain within IL-2R beta (amino acid residues 267-312). (jimmunol.org)
  • A powerful chemical modification procedure has been developed to define determinants of DNA recognition by the p50 subunit of NF-kappa B. Differential labelling with [14C] iodoacetate has identified a conserved cysteine residue, Cys62, that was protected from modification by the presence of an oligonucleotide containing the specific recognition site of the protein. (epfl.ch)
  • Thus the sulphydryl group of Cys62 is an important determinant of DNA recognition by the p50 subunit of NF-kappa B. (epfl.ch)
  • Here we report that when mice lacking the RelA subunit of NF-kappaB are brought to term by breeding onto a tumor necrosis factor receptor (TNFR)1-deficient background, the trice that are born lack lymph nodes, foyer's patches, and an organized splenic microarchitecture, and have a profound defect in T cell-dependent antigen responses. (caltech.edu)
  • On activation of TLR, subsequent signalling of the cells can activate the master kinase called the Ikappa-B kinase (IκK), which phosphorylates the Ikappa-B alpha (IκBα) subunit of NF-κB. (biomedcentral.com)
  • NRG-1 also prevented the nuclear translocation of the NF-kB p65 subunit following LPS administration. (biomedcentral.com)
  • However, NRG-1 increased production of the neuroprotective cytokine granulocyte colony-stimulating factor (G-CSF) and the nuclear translocation of the NF-kB p52 subunit, which is associated with the induction of anti-apoptotic and suppression of pro-inflammatory gene expression. (biomedcentral.com)
  • NEMO is a subunit of the IκB kinase complex that activates NF-κB. (wikipedia.org)
  • In the absence of regulatory subunit IKK-γ the IKK complex is inactive, preventing the downstream signal transduction cascade leading to NF-κB activation. (wikipedia.org)
  • The NF-kappa B family of transcription proteins represents multiple DNA binding, rel related polypeptides that contribute to regulation of genes involved in immune responsiveness and inflammation, as well as activation of the HIV long terminal repeat. (nih.gov)
  • Various cellular stimuli relieve this inhibition by mechanisms largely unknown, leading to NF-kappa B nuclear localization and transactivation of its target genes. (pnas.org)
  • The data may explain the kainate-induced cell surface expression of major histocompatibility complex class I molecules, which are encoded by genes known to be controlled by NF-kappa B. Moreover, NF-kappa B activity was found to change dramatically in neurons during development of the cerebellum between days 5 and 7 after birth. (nih.gov)
  • ICA upregulated the expression of SIRT6 and had an inhibitory effect on NF- κ B inflammatory signaling pathways as shown by decreasing mRNA levels of the NF- κ B downstream target genes TNF- α , ICAM-1, IL-2, and IL-6. (hindawi.com)
  • Given the role of NF-κB-related genes in cell proliferation, invasiveness, angiogenesis and inflammation, we postulated that they might be deregulated in IBC. (pubmedcentralcanada.ca)
  • We measured the mRNA expression levels of 60 NF-κB-related genes by using real-time quantitative RT-PCR in a well-defined series of 35 IBCs, by comparison with 22 stage IIB and III non inflammatory breast cancers. (pubmedcentralcanada.ca)
  • Thirty-five (58%) of the 60 NF-κB-related genes were significantly upregulated in IBC compared with non IBC. (pubmedcentralcanada.ca)
  • We identified a five-gene molecular signature that matched patient outcomes, consisting of IL8 and VEGF plus three NF-κB-unrelated genes that we had previously identified as prognostic markers in the same series of IBC. (pubmedcentralcanada.ca)
  • Some upregulated NF-κB-related genes might serve as novel therapeutic targets in IBC. (pubmedcentralcanada.ca)
  • These 109 genes, some of which were NF-κB-related, were mainly associated with signal transduction, cell motility, invasion, angiogenesis and local inflammatory processes. (pubmedcentralcanada.ca)
  • Another genome-wide expression profiling study comparing 16 IBCs with 18 non stage-matched non IBCs identified a large number of overexpressed NF-κB-related genes [ 10 ]. (pubmedcentralcanada.ca)
  • Nuclear factor-kappa B (NF-kappa B) is the generic name of a family of transcription factors that function as dimers and regulate genes involved in immunity, inflammation and cell survival. (kegg.jp)
  • In this study, we asked whether the multiunit transcription factor, nuclear factor (NF)-kappa B, which regulates the expression of genes involved in defense and immune processes, is activated in airway epithelial cells following stimulation with inflammatory mediators and hydrogen peroxide. (ersjournals.com)
  • These results suggest that NF-kappa B may represent an important transcription factor, controlling the expression of cytokine genes in airway epithelial cells. (ersjournals.com)
  • Nuclear factor κ B (NF-κB) transcription factors are important candidates in modulating the expression of these genes. (endocrine-abstracts.org)
  • The aim of our research is to determine if NF-κB factors are maybe involved in the regulation of endothelial angiogenesis-related genes and thus in ovarian angiogenesis. (endocrine-abstracts.org)
  • O NF- k B é um fator de transcrição envolvido no controle da expressão de diversos genes ligados à resposta inflamatória. (usp.br)
  • O NF- k B e os IFNGR1 e INFGR2 são necessários para a expressão dos genes NCF1 e NCF2 e para a ativação do sistema NADPH oxidase humano neste sistema modelo. (usp.br)
  • The NF- k B is a transcriptional factor involved in the expression of several genes related to the inflammatory response. (usp.br)
  • We studied the NF- k B and the IL-12/23-IFN- g axis defects consequences on the regulation of CYBA, NCF1, NCF2 and NCF4 genes of the human NADPH oxidase system in U937 cells, and in B EBV cells from patients with EDA-ID, DGC, or patients with IL-12/23-IFN- g axis defects. (usp.br)
  • We show here that NF-kappa B, an important regulator of numerous cytokine genes, is functionally inhibited by the synthetic glucocorticoid dexamethasone (DEX). (asm.org)
  • Nuclear factor kappa B (NF-kappa B) is a critical regulator of several genes which are involved in immune and inflammation responses. (asm.org)
  • Following cardiopulmonary bypass (CPB) and cardiac global ischemia and reperfusion, proinflammatory genes are up-regulated, and nuclear factor (NF)-kappaB is involved in this regulation. (semanticscholar.org)
  • Synaptic activation of hippocampal neurons is known to trigger retrograde transport of transcription factor NF-kappa B. Transcription factors of the NF-kappa B family are widely expressed in the nervous system and regulate expression of several genes involved in neuroplasticity, cell survival, learning and memory. (uni-bielefeld.de)
  • Activation of NF- kB is a rapid, immediate early (IE) event that occurs within minutes after exposure to a relevant inducer, does not require de novo protein synthesis, and results in a strong transcriptional stimulation of several early viral as well as cellular genes. (lymerick.net)
  • Activation of NF- kB constitutes an obvious target because many of its target genes growth factors, cytokines and their receptors, and proto- oncogenes profoundly influence the host cell cycle. (lymerick.net)
  • Nf kappa dimerizes with other members the kappa brel family regulate expression genes that participate immune apoptotic and oncogenic processes. (informe.com)
  • Our studies show that when compared to LNCaP, NF-κB activity is significantly higher in C4-2B and PC3, and that the activation of NF-κB signaling in prostate cancer cells resulted in the increased expression of the osteoclast inducing genes PTHrP and RANKL. (ox.ac.uk)
  • These results indicate that osteoclastic reaction is required even in the osteoblastic cancer cells and the activation of NF-κB signaling in prostate cancer cells increases osteoclastogenesis by up-regulating osteoclastogenic genes, thereby contributing to bone metastatic formation. (ox.ac.uk)
  • As the human ocular surface is heavily colonised by gram-positive cocci bacteria, a balance of activation/repression of NF-κB target genes is essential to avoid uncontrolled infection or autoimmune-related inflammation. (biomedcentral.com)
  • NF-kappa B (NF-kB) was identified as a potential transcriptional regulator of NRG-1-suppressed genes following ischemia. (biomedcentral.com)
  • Furthermore, PPAR gamma activation by rosiglitazone strongly suppresses cytokine-induced transcript levels of the NF-kappa B-dependent genes intracellular adhesion molecule 1 (ICAM-1) and CXCL1 ( KC), the murine homolog of IL-8, in myotubes. (maastrichtuniversity.nl)
  • NF- em /em B also regulates many genes encoding protein with anti-apoptotic properties, including cFLIP,36 that may. (sunolmolecular.com)
  • Binding of IKK-γ to IKK-α and IKK-β subunits activates the IKK complex leading to phosphorylation of IκB kinase, IκBα, and release of NF-κB dimers p105 and RELA to translocate to the nucleus and activate transcription of NF-κB responsive genes. (wikipedia.org)
  • In the presence of the NBD peptide, the IKK complex remains inactive and IκBα sequesters NF-κB dimers in the cytoplasm inhibiting transcription of NF-κB responsive genes. (wikipedia.org)
  • Protein kinase C-zeta mediates NF-kappa B activation in human immunodeficiency virus-infected monocytes. (asm.org)
  • Although little information as to what signal transduction pathways mediate NF-kappa B activation in monocytes-macrophages is available, our previous work indicated that classical protein kinase C (PKC) isoenzymes were not involved in the HIV-mediated NF-kappa B activation. (asm.org)
  • NF-kappa-B-activating kinase Monoclonal detects proteins from variouse species most likely human. (antibody-antibodies.com)
  • The ubiquitously expressed transcription factor NF-kappa B and the serine-threonine kinase Akt both are involved in the promotion of cell survival. (elsevier.com)
  • Indeed, I kappa B kinase, the kinase involved in NF-kappa B activation, is a substrate of Akt, and activation of Akt therefore stimulates NF-kappa B activity. (elsevier.com)
  • On the other hand TNF-mediated NF-kappa B activation is not reduced by the phosphoinositide-3 kinase inhibitors wortmannin and LY294002, although these inhibitors completely block the activation of Akt. (elsevier.com)
  • Kato T, Delhase M, Hoffmann A, Karin M (2003) CK2 is a C-terminal IκB kinase responsible for NF-κB activation during the UV response. (springer.com)
  • The effect of the NF-kappa B inhibitors curcumin and lactacystin on myogenic differentiation of rhabdomyosarcoma cells. (biomedsearch.com)
  • Reporting in Molecular Cancer Therapeutics , the researchers found that inhibitors of NF-kappa B not only protected against radiation toxicity when given before exposure to treatment, but also lessened the radiation toxicity when given one to two hours post-exposure. (medicalxpress.com)
  • In the study, both NF-kappa B inhibitors and proteasome inhibitors were examined for their potential to alleviate the negative effects of radiation. (medicalxpress.com)
  • Although proteasome inhibitors demonstrate activity against NF-kappa B, they also target many other pathways," said Ulrich Rodeck, M.D., Ph.D., professor of Dermatology and Cutaneous Biology at Jefferson Medical College of Thomas Jefferson University. (medicalxpress.com)
  • Because NAC and PDTC are among the most effective inhibitors of the transcription factor NF-kappa B, we examined SV's ability to activate NF-kappa B before the onset of morphologic or biochemical evidence of apoptosis. (rupress.org)
  • Pam3CSK4-stimulated NF-κB activation was inhibited by IκK inhibitors, Wedelolactone and BMS-345541. (biomedcentral.com)
  • Treatment with two pharmacological inhibitors of NF-kappa B, SN50 and N-tosyl-l-phenylalanine chloromethyl ketone (TPCK), blocks TNF-induced Akt activation. (elsevier.com)
  • Hatada EN, Nieters A, Wulczyn FG, Naumann M, Meyer R, Nucifora G, …, Scheidereit C (1992) The ankyrin repeat domains of the NF-kappa B precursor p105 and the protooncogene bcl-3 act as specific inhibitors of NF-kappa B DNA binding. (springer.com)
  • Tumor necrosis factor and interleukin-1 lead to phosphorylation and loss of I kappa B alpha: a mechanism for NF-kappa B activation. (asm.org)
  • The objective of this study was to elucidate the role of quercetin in modulating leptin-induced inflammation as assessed by the levels of Ob-Ra expression, ERK1/2 phosphorylation, NF-kappa B activation and TNF-alpha secretion in umbilical vein endothelial cells (HUVECs) in vitro . (biomedcentral.com)
  • Ob-Ra expression, ERK1/2 phosphorylation, NF-kappa B activation and TNF-alpha secretion were quantified by ELISA, and NF-kappa B activationby immunofluorescence staining. (biomedcentral.com)
  • The aim of this study was to investigate the effect of quercetin in modulating the expression of Ob-Ra, phosphorylation of ERK1/2, activation of NFκB and secretion of TNFα in leptin-induced human umbilical vein endothelial cells (HUVECs) in vitro . (biomedcentral.com)
  • Of rel and nfkappa relationship with kappa beta and regulation phosphorylation. (informe.com)
  • Tumor necrosis factoralpha activation nfkappa requires the phosphorylation of. (informe.com)
  • Although these results place Akt upstream of NF-kappa B activation in the sequence of signaling events, we report that this may not necessarily be the case and that Akt is a downstream target of NF-kappa B. Treatment of NIH3T3 cells with the NF-kappa B activators, tumor necrosis factor (TNF) alpha and lipopolysaccharide, results in the stimulation of Akt phosphorylation. (elsevier.com)
  • The nuclear translocation of p65 and increased DNA binding activity of NF-kappa B also precede Akt phosphorylation. (elsevier.com)
  • Consistent with this conclusion is the finding that overexpression of p65/RelA leads to Akt phosphorylation in the absence of extracellular stimulatory factors, whereas overexpression of I kappa B-alpha reduces Akt phosphorylation below basal levels. (elsevier.com)
  • As shown in the top panel of Figure 2 , IKK activity, as assessed by phosphorylation of GST-I-kappa B-alpha, was increased at 15 min after addition of ferrous iron. (biomedcentral.com)
  • Karin M, Ben-Neriah Y (2000) Phosphorylation meets ubiquitination: the control of NF-κB activity. (springer.com)
  • NF-kappaB transcription factors and the signaling pathways that activate them play a critical role in cancer development, progression and therapy, and recently have become a focal point for intense drug discovery and development efforts. (nih.gov)
  • Moreover, our studies suggest crosstalk between NF[kappa]B and c-Jun/AP-1 pathways in cellular response to Cr(VI) exposure for COX-2 induction. (thefreelibrary.com)
  • There are several pathways leading to NF-kappa B-activation. (kegg.jp)
  • The Zi Qi decoction inhibited liver fibrosis by inhibiting the TLR4-related NF-kB and MAPK signaling pathways and preventing activation of HSCs. (medscimonit.com)
  • Altogether, these results suggest that atypical PKC isoenzymes, including PKC-zeta, participate in the signal transduction pathways by which HIV infection results in the activation of NF-kappa B in human monocytic cells and macrophages. (asm.org)
  • Here, we have compared the contribution of the type 1 (p50-dependent) and type 2 (p52-dependent) NF-kappaB activation pathways to cell survival, proliferation, homotypic aggregation, and specific gene regulation of murine primary B lymphocytes. (caltech.edu)
  • Overall, our studies suggest that both type 1 and type 2 NF-kappaB pathways contribute to the gene expression and biological program unique for CD40 in B cell activation. (caltech.edu)
  • Evodiamine-induced human melanoma A375-S2 cell death was mediated by PI3K/Akt/caspase and Fas-L/NF-kappaB signaling pathways and augmented by ubiquitin-proteasome inhibition. (semanticscholar.org)
  • NF-kappaB Signaling Pathways in Neurological Inflammation: A Mini Review. (uni-bielefeld.de)
  • Reducing effect of IL-32α in the development of stroke through blocking of NF-κB, but enhancement of STAT3 pathways. (uni-bielefeld.de)
  • Neuroprotective and anti-inflammatory effects of NRG-1 are associated with the differential regulation of NF-kB signaling pathways in microglia. (biomedcentral.com)
  • We as a result anticipate that signaling pathways induced by reovirus binding provides about the inhibition of NF- em /em B noticed following T3 an infection. (sunolmolecular.com)
  • Although initially believed to operate as components of distinct signaling pathways, several studies have demonstrated that the NF-kappa B and Akt signaling pathways can converge. (elsevier.com)
  • Silverman N, Maniatis T (2001) NF-κB signaling pathways in mammalian and insect innate immunity. (springer.com)
  • Heterodimerization and transcriptional activation in vitro by NF-kappa B proteins. (nih.gov)
  • These experiments emphasize the role of NF-kappa B dimerization as a distinct level of transcriptional control that may permit functional diversification of a limited number of regulatory proteins. (nih.gov)
  • NF kappa B Activators offered by Santa Cruz activate NF kappa B and, in some cases, other transcription factors and apoptosis related proteins. (scbt.com)
  • This factor has a DNA-binding specificity similar to that of NF-kappa B but is unrelated to this or other Rel proteins by functional and biochemical criteria. (epfl.ch)
  • I kappa BNS blocks transcription from NF-kappa B reporters, alters NF-kappa B electrophoretic mobility shifts, and interacts with NF-kappa B proteins in thymic nuclear lysates following TCR stimulation. (ucm.es)
  • The NFKB complex is inhibited by I-kappa-B proteins (NFKBIA, MIM 164008 or NFKBIB, MIM 604495), which inactivate NFKB by trapping it in the cytoplasm. (biomol.com)
  • NF{kappa}B-dependent down-regulation of tumor necrosis factor receptor-associated proteins contributes to interleukin-1-mediated enhancement of ultraviolet B-induced apoptosis. (semanticscholar.org)
  • NF-κB, a heterodimer consisting mainly of p65 and p50 proteins, functions as a transcription factor that induces inflammatory cytokines and antiapoptotic proteins. (biomedcentral.com)
  • A growing body of evidence indicates that the activation of NF-κB is associated with resistance to apoptosis, expression of angiogenic proteins, and carcinogenesis due to its fundamental effects on cellular dedifferentiation and proliferation in malignancies [ 3 , 4 ]. (biomedcentral.com)
  • The interaction relnfkb proteins with dna requires.Preferential role for nfkappa brel signaling the type but not type celldependent immune response vivo. (informe.com)
  • NF-kappa B-mediated repression of growth arrest- and DNA-damage-inducible proteins 45alpha and gamma is essential for cancer cell survival. (scienceexchange.com)
  • Here, we report that combined down-regulation of growth arrest- and DNA-damage-inducible proteins (GADD)45alpha and gamma expression by NF-kappaB is an essential step for various cancer types to escape programmed cell death. (scienceexchange.com)
  • Virus-induced activation of nuclear factor-kappa B (NF-and in target tissues was purchased from Invitrogen and was utilized at a concentration of 100 ng/ml. had been assayed for NF-(Santa Cruz # 203) and cFLIP (GeneTex # GTX26144) which recognizes the 55kD cFLIPL (Turn alpha) proteins. (sunolmolecular.com)
  • Debate The NF-1 as well as the nonstructural proteins 1s both which may donate to apoptosis in reovirus-infected 4-Methylumbelliferone cells. (sunolmolecular.com)
  • EMSAs using a probe containing this NF-kappaB binding sequence and chromatin immunoprecipitation indicated that p65/p50 and p50/p50 dimers were the main NF-kappaB/Rel proteins involved in STAT-4 gene expression in maturing DC. (archives-ouvertes.fr)
  • Ghosh S, May MJ, Kopp EB (1998a) NF-κB and Rel proteins: evolutionarily conserved mediators of immune responses. (springer.com)
  • Viral protein involved in the activation of host NF-kappa-B. This protein is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. (uniprot.org)
  • Activation of cells with appropriate stimuli results in the dissociation of NF-kappa B from I kappa B and its translocation to the nucleus as an active binding protein. (pnas.org)
  • Also considered to be a mediator for TAX activation of NF-kappa-B. Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity. (rcsb.org)
  • the interaction promotes TNIP1 -dependent 'Lys-27'-linked polyubiquitination of IKBKG which perturbs NF-kappa-B activation during bacterial infection. (rcsb.org)
  • Curcumin (diferuloylmethane) inhibits receptor activator of NF-kappa B ligand-induced NF-kappa B activation in osteoclast precursors and suppresses osteoclastogenesis. (greenmedinfo.com)
  • Treatment of these cells with RANKL activated NF-kappaB, and preexposure of the cells to curcumin completely suppressed RANKL-induced NF-kappaB activation. (greenmedinfo.com)
  • Thus overall these results indicate that RANKL induces osteoclastogenesis through the activation of NF-kappaB, and treatment with curcumin inhibits both the NF-kappaB activation and osteoclastogenesis induced by RANKL. (greenmedinfo.com)
  • It is demonstrated here with human T lymphocytes and monocytes that different stimuli, including tumor necrosis factor alpha and phorbol 12-myristate 13-acetate, cause rapid degradation of I kappa B-alpha, with concomitant activation of NF-kappa B, followed by a dramatic increase in I kappa B-alpha mRNA and protein synthesis. (pnas.org)
  • The activation of NF-kappa B could be blocked with the antioxidant pyrrolidine dithiocarbamate, suggesting the involvement of reactive oxygen intermediates. (nih.gov)
  • NF-B activation profile was evaluated in cutaneous biopsies from 47 patients with clinical and laboratorial diagnosis of leprosy followed at a referral center for treatment of leprosy, the leprosy outpatient clinic of the Hospital of Clinics of Faculty of Medicine of Ribeirão Preto University of São Paulo. (usp.br)
  • NF-B activation index (ranging from 0 to 4) was calculated according to the percentage of positivity in Southwestern histochemistry. (usp.br)
  • Borderline and pure neural leprosy clinical forms were associated with NF-B activation, with odds ratio of 44 (p=.014) and 30 (p=.029), respectively. (usp.br)
  • NF-B activation was correlated with in situ detection of tumor necrosis factor- by immunohistochemistry (p=.0064). (usp.br)
  • Great variation of NF-B activation was found in clinical forms of leprosy. (usp.br)
  • NF-B activation was present in clinical forms with increased susceptibility (multibacillary) and immunological instability (borderline), which suggests favorable conditions towards infection, probably due to the anti-apoptotic effects of NF-B, since bacillary survival is dependent of cellular functions. (usp.br)
  • IL-2-induced signal transduction involves the activation of nuclear NF-kappa B expression. (jimmunol.org)
  • IL-2 activation of nuclear NF-kappa B expression is regulated in part at a post-translational level, involving the rapid translocation of both the 50- and 65-kDa subunits of NF-kappa B from the cytoplasm to the nucleus. (jimmunol.org)
  • Together, these findings suggest that NF-kappa B may play an important role as one intracellular second messenger relaying signals from the plasma membrane to cell nucleus that leads to IL-2-induced activation and growth. (jimmunol.org)
  • Exposure of mammalian cells to radiation triggers the ultraviolet (UV) response, which includes activation of activator protein-1 (AP-1) and nuclear factor kappa B (NF-kappa B). This was postulated to occur by induction of a nuclear signaling cascade by damaged DNA. (sciencemag.org)
  • Because inactive NF-kappa B is stored in the cytosol, analysis of its activation directly tests the involvement of a nuclear-initiated signaling cascade. (sciencemag.org)
  • Enucleated cells are fully responsive to UV both in NF-kappa B induction and in activation of another key signaling event. (sciencemag.org)
  • Our results show that p65 and c-Jun are two major components involved in NF[kappa]B and AP-1 activation, respectively. (thefreelibrary.com)
  • Synergistic transcriptional activation of the IL-8 gene by NF-kappa B p65 (RelA) and NF-IL-6. (jimmunol.org)
  • Maximal transcriptional activation by PMA in Jurkat T lymphocytes was shown to require intact binding sites for both NF-kappa B and NF-IL-6. (jimmunol.org)
  • Transient cotransfection analyses indicate that the cooperative association of NF-IL-6 and RelA with the IL-8 promoter results in synergistic transcriptional activation. (jimmunol.org)
  • Mutational analyses of RelA demonstrate that the C-terminal transactivation domain and the DNA binding domain are required for synergistic activation with NF-IL-6. (jimmunol.org)
  • These data demonstrate that RelA and members of the C/EBP/NF-IL-6 family can functionally cooperate in transcriptional activation of the IL-8 gene and suggest a common mechanism for inducible regulation of cytokine gene expression. (jimmunol.org)
  • Since activation of NF-kappa B by extracellular stimuli is implicated in inflammation, infection and cancer induction, as well as in protection of cells against insult, it will be important in subsequent studies to elucidate whether heavy ion-induced NF-kappa B activation is involved in downstream gene expression. (biomedsearch.com)
  • Activation of NF-kappa B in the SV40 transformed human tracheobronchial epithelial cell line 1HAEo- was measured by electrophoretic mobility shift assays. (ersjournals.com)
  • Exposure to H2O2 platelet activating factor (PAF) and lipopolysaccharide (LPS) did not lead to increased NF-kappa B activation. (ersjournals.com)
  • Co-stimulation of IL-1 beta with H2O2 led to augmentation and prolongation of the effect on NF-kappa B activation compared to stimulation with IL-1 beta alone. (ersjournals.com)
  • According to Dr. Rodeck, the key is to downmodulate the NF-kappa B activity, rather than ablating it completely, as excessive NF-kappa B activation is potentially detrimental even in the absence of radiation therapy. (medicalxpress.com)
  • The role of nuclear factor kappa B (NF- k B) and the IL-12/23-IFN- g axis in the activation of the NADPH oxidase system. (usp.br)
  • The NF- k B and the IFNGR1 and INFGR2 are necessary for NCF1 and NCF2 gene expression and activation of the human NADPH oxidase in this model system. (usp.br)
  • In transfection experiments, DEX treatment in the presence of cotransfected glucocorticoid receptor (GR) inhibits NF-kappa B p65-mediated gene expression and p65 inhibits GR activation of a glucocorticoid response element. (asm.org)
  • In addition, we demonstrate that the ability of p65, p50, and c-rel subunits to bind DNA is inhibited by DEX and GR. In HeLa cells, DEX activation of endogenous GR is sufficient to block tumor necrosis factor alpha or interleukin 1 activation of NF-kappa B at the levels of both DNA binding and transcriptional activation. (asm.org)
  • PKC-zeta belongs to this family and is known to be an important step in NF-kappa B activation in other cell systems. (asm.org)
  • The HIV-mediated NF-kappa B activation is selectively reduced by AO to PKC-zeta. (asm.org)
  • NF-kappa B, consisting of a 50-kDa protein (p50) and a 65-kDa protein (p65), is bound to a cytoplasmic retention protein called I kappa B. Stimulation of cells with a variety of inducers, including cytokines such as tumor necrosis factor and interleukin-1, leads to the activation and the translocation of p50/65 NF-kappa B into the nucleus. (asm.org)
  • We also show that both I kappa B alpha loss and NF-kappa B activation are inhibited in the presence of antioxidants, demonstrating that the loss of I kappa B alpha is a prerequisite for NF-kappa B activation. (asm.org)
  • We propose a mechanism for the activation of NF-kappa B through the modification and loss of I kappa B alpha, thereby establishing its role as a mediator of NF-kappa B activation. (asm.org)
  • Together, these studies demonstrate for the first time the requirement for Gli in Kras- dependent pancreatic epithelial transformation, implicate a novel mechanism of Gli-NF-\(\kappa\)B oncogenic activation, and provide genetic evidence supporting the therapeutic targeting of Gli activity in pancreatic cancer. (harvard.edu)
  • Further support for the predicted effect of PAPPA on HCC cells came from both in vitro studies that showed PAPPA to contribute to the activation of NF kappa B signaling, and clinical data, which linked higher expression levels of PAPPA to advanced stage HCC. (uni-muenchen.de)
  • The eukaryotic transcription factor nuclear factor-kappa B (NF-kappa B) participates in many parts of the genetic program mediating T lymphocyte activation and growth. (sciencemag.org)
  • Phorbol ester and tumor necrosis factor-alpha induction of nuclear NF-kappa B is associated with both the degradation of performed I kappa B alpha and the activation of I kappa B alpha gene expression. (sciencemag.org)
  • TL1A induces NF-κB activation in EC in renal and cardiac tissue from wild type but not DR3 knock-out mice. (biomedcentral.com)
  • Over-expression of bcl-2 in AT-3 cells, which has been shown to inhibit SV-induced apoptosis, also inhibits SV-induced NF-kappa B activation. (rupress.org)
  • The metal chelator and anti-oxidant pyrollidine dithiocarbamate (PDTC) has been used extensively in studies implicating reactive oxygen intermediates in the activation of nuclear factor kappa B (NF kappa B). In agreement with other studies, we have shown that PDTC inhibits NF kappa B activation in response to the pro-inflammatory cytokines interleukin 1 (IL1) and tumour necrosis factor (TNF). (tcd.ie)
  • On the basis of these results we suggest that, while NF kappa B activation is unaffected by PDTC, DNA binding is inhibited through a mechanism involving a shift towards oxidizing conditions, and that this is the mechanism of action of both PDTC and diamide in the cells tested here. (tcd.ie)
  • Inhibition of NF-kappa B activation can attenuate ischemia/reperfusion-induced contractility impairment via decreasing cardiomyocytic proinflammatory gene up-regulation and matrix metalloproteinase expression. (semanticscholar.org)
  • We studied whether inactivation of NF-kappaB could decrease myocardial ischemia/reperfusion injury with cardioplegia during CPB, attenuate matrix metalloproteinase (MMP) activation, and prevent cardiac mechanical dysfunction. (semanticscholar.org)
  • Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti. (moldiag.com)
  • There was a distinct change in the activation level of NF-κB between T24 and T24PR cells, suggesting strong nuclear localization of NF-κB could be a promising target after developing acquired platinum-resistance in bladder cancer. (biomedcentral.com)
  • The mechanism by which DHMEQ inhibits activation of NF-κB is unique because DHMEQ inhibits NF-κB translocation from the cytoplasm to the nucleus [ 7 ]. (biomedcentral.com)
  • Here we report L.plantarum tested to induce the NF -κB activation or expression in HEK 293 cell lines in a time - and dose-dependent manner. (ijpbs.net)
  • Activation of NF -κB through Heat killed bacteria was confirmed by fold change in HEK-293 cell lines. (ijpbs.net)
  • Luciferase gene reporter analyses assay experiments demonstrated that NF -κB activation is seen in HEK-293 cell lines through Heat killed cells of L.plantarum. (ijpbs.net)
  • Vimentin and PSF act in concert to regulate IbeA+ E. coli K1 induced activation and nuclear translocation of NF-κB in human brain endothelial cells. (uni-bielefeld.de)
  • I suppose it is because Babesia hasn t been investigated regarding NF- kB activation yet, since above two piroplasmatic 'cousins' Malaria and Theileria does induce NF- kB , there is reason to suspect that Babesia also knows the same trick. (lymerick.net)
  • In this manuscript we summarize current knowledge about the structure and the functions of NF-κB components and mechanisms of their activation and importance in CLL. (studylibpl.com)
  • Activation nfkappa brel and. (informe.com)
  • It has been proven that nfkappa activation happens prior the transcription. (informe.com)
  • The activation select subset nfkappa nfkappab pleiotropic transcription factor which present almost. (informe.com)
  • Didonato lin activation nfkappa required for hypertrophic. (informe.com)
  • Activation nfkappa antineoplastic agents. (informe.com)
  • Human tcell leukemia virus type tax activation nfkappa brel involves. (informe.com)
  • Inducible nitric oxide synthase expression and nuclear transcription factor kappa activation. (informe.com)
  • Activation of NF-kappa B signaling promotes growth of prostate cancer cells in bone. (ox.ac.uk)
  • Although many studies indicate that the activation of NF-κB signaling appears to be correlated with advanced cancer and promotes tumor metastasis by influencing tumor cell migration and angiogenesis, the influence of altered NF-κB signaling in prostate cancer cells within boney metastatic lesions is not clearly understood. (ox.ac.uk)
  • while the activation of NF-κB signaling in LNCaP cells promoted tumor establishment and proliferation in the bone. (ox.ac.uk)
  • The activation of NF-κB in LNCaP cells resulted in the formation of an osteoblastic/osteoclastic mixed tumor with increased osteoclasts surrounding the new formed bone, similar to metastases commonly seen in patients with prostate cancer. (ox.ac.uk)
  • It is advantageous to test NF-κB targeting molecules in an ocular surface culture system that allows assessment of temporal NF-κB activation in a longitudinal fashion without destruction of cells. (biomedcentral.com)
  • This study aims to establish an in-vitro cell culture system to assess NF-κB activation in the context of ocular surface cells. (biomedcentral.com)
  • We aim to describe the activation of NF-κB in an in-vitro system of ocular surface cells using promoter assay and other approaches, induced by the presence of a TLR2 ligand. (biomedcentral.com)
  • In normal cells exposed to stress, the central transcription factor NF-κB is activated only transiently, to modulate the activation of downstream immune responses. (ch3biosystems.com)
  • Skeletal muscle pathology associated with a chronic inflammatory disease state ( e. g., skeletal muscle atrophy and insulin resistance) is a potential consequence of chronic activation of NF-kappa B. It has been demonstrated that peroxisome proliferator-activated receptors (PPARs) can exert anti-inflammatory effects by interfering with transcriptional regulation of inflammatory responses. (maastrichtuniversity.nl)
  • The goal of the present study, therefore, was to evaluate whether PPAR activation affects cytokine-induced NF-kappa B activity in skeletal muscle. (maastrichtuniversity.nl)
  • Using C2C12 myotubes as an in vitro model of myofibers, we demonstrate that PPAR, and specifically PPAR gamma, activation potently inhibits inflammatory mediator-induced NF-kappa B transcriptional activity in a time- and dose-dependent manner. (maastrichtuniversity.nl)
  • To verify whether muscular NF-kappa B activity in human subjects is suppressed by PPAR gamma activation, we examined the effect of 8 wk of rosiglitazone treatment on muscular gene expression of ICAM-1 and IL-8 in type 2 diabetes mellitus patients. (maastrichtuniversity.nl)
  • These findings demonstrate that muscle-specific inhibition of NF-kappa B activation may be an interesting therapeutic avenue for treatment of several inflammation-associated skeletal muscle abnormalities. (maastrichtuniversity.nl)
  • Cells had been incubated over night at 4C with antibodies aimed against NF- 0.001 at 48 h) and caspase 3 activation assays ( 0.001) (Shape 1). (sunolmolecular.com)
  • Altogether, these results indicate that STAT-4 can be finely tuned along with DC maturation through NF-kappaB activation and that its induction may be involved in preparing the DC to be receptive to the cytokine environment present in lymphoid organs. (archives-ouvertes.fr)
  • These results suggest that NF-kappa B is required for TNF-mediated Akt activation and that it lies upstream of the stimulation of Akt. (elsevier.com)
  • Research in our laboratory suggests that iron also plays a pivotal role in intracellular signaling for NF-kappa B activation in hepatic macrophages (HM). (biomedcentral.com)
  • 4) iron directly induced TNF-alpha expression via IKK and NF-kappa B activation in normal HM. (biomedcentral.com)
  • We propose that iron acts as an independent proinflammatory molecule via induction of the intracellular signaling for NF-kappa B activation in HM and primes the liver for chronic inflammation and injury. (biomedcentral.com)
  • The most intriguing and critical finding from these cellular or animal model experimentations, was that activation of NF-kappa B was tightly correlated with the increased non-heme iron content in HM, suggesting the priming role of iron in NF-kappa B activation and proinflammatory cytokine expression by HM in alcoholic liver disease. (biomedcentral.com)
  • The timing of IKK activation preceded a disappearance of cytosolic I-kappa B-alpha and an increase in the nuclear level of p65 at 30~45 min. (biomedcentral.com)
  • Thus, these results unequivocally demonstrate that ferrous iron can directly and selectively stimulates the signaling leading to IKK and NF-kappa B activation in cultured HM. (biomedcentral.com)
  • S-nitrosylation of FLICE inhibitory protein determines its interaction with RIP1 and activation of NF-kappa B. (cdc.gov)
  • A drug called NEMO Binding Domain (NBD) has been designed to inhibit activation of NF-κB. (wikipedia.org)
  • Additionally, NF-κB activation was suppressed in HeLa cells after incubation with NBD wild type peptides. (wikipedia.org)
  • NF-kappa-B-activating protein is a protein that in humans is encoded by the NKAP gene. (wikipedia.org)
  • The NK-kappa B transcription factor complex is sequestered in the cytoplasm by the inhibitory protein I kappa B-alpha (MAD-3). (pnas.org)
  • Transfection studies reveal that the I kappa B-alpha mRNA and the encoded protein are potently induced by NF-kappa B and by homodimers of p65 and of c-Rel. (pnas.org)
  • Western analysis showed that ICA upregulated SIRT6 protein expression and downregulated NF- κ B (p65) protein expression in animal tissues and cell models. (hindawi.com)
  • The predicted protein contains seven ankyrin repeats and is homologous to I kappa B family members. (ucm.es)
  • Human NF B p50 (NFKB1) peptide corresponding to a region near the N-terminus of the human protein conjugated to KLH. (lsbio.com)
  • Both acute (24 h) and chronic (10-20 week) exposure of human fibroblast cells to low dose sodium arsenite (As(III)) significantly affects activating protein-1 (AP-1) and nuclear factor kappa B (NF-kappaB) DNA binding activity. (edu.au)
  • Chronic exposure to 0.1 or 0.5 muM As(III) decreased c-Jun, c-Fos and Ref-1 protein levels and AP-1 and NF-KB binding activity, but increased Trx expression. (edu.au)
  • Furthermore, as discussed below, viral oncogene products, including human T-cell leukemia virus type 1 (HTLV-1) Tax protein and Epstein-Barr virus latent infection membrane protein 1 ( EBV LMP1), each act by unique mechanisms to disrupt NF- kB regulation and initiate viral transformation. (lymerick.net)
  • NF-κB is a protein complex that becomes activated in response to inflammatory stimuli and has been linked to cancer. (healthblogs.org)
  • Significantly higher levels of NF-kappa B and Mn-SOD (both their protein level and their activity) were found in breast cancer patients before and after CAF therapy, in comparison with healthy women. (ac.rs)
  • Whether curcumin inhibits RANKL-induced osteoclastogenesis through suppression of NF-kappaB was also confirmed independently, as RANKL failed to activate NF-kappaB in cells stably transfected with a dominant-negative form of IkappaBalpha and concurrently failed to induce osteoclastogenesis. (greenmedinfo.com)
  • Inhibits NF-kappa-B by complexing with and trapping it in the cytoplasm. (sdsc.edu)
  • We demonstrate that overexpression of dynamitin, which is known to dissociate dynein from microtubules, and treatment with microtubule-disrupting drugs inhibits nuclear accumulation of NF-kappa B p65 and reduces NF-kappa B-dependent transcription activity. (uni-bielefeld.de)
  • Propofol inhibits proliferation and induces neuroapoptosis of hippocampal neurons in vitro via downregulation of NF-κB p65 and Bcl-2 and upregulation of caspase-3. (uni-bielefeld.de)
  • NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. (lsbio.com)
  • Moreover NF-κB ability to inhibition of apoptosis, induction of proliferation and angiogenesis suggest that NF-κB could be very significant in oncogenesis and tumor progression. (studylibpl.com)
  • We demonstrate that inhibition of NF-kappaB in cancer cells results in GADD45alpha- and gamma-dependent induction of apoptosis and inhibition of tumor growth. (scienceexchange.com)
  • NF-kB is a key transcription factor that is involved in immune and inflammatory responses, developmental processes, cellular growth and apoptosis. (abeomics.com)
  • These outcomes demonstrate that NF-0.001) increased T1L induced-apoptosis from 21 to 41% (Amount 7D). (sunolmolecular.com)
  • NF- em /em B legislation is thus more likely to possess implications for loss of life ligand-mediated apoptosis and disease caused by a number of viral attacks. (sunolmolecular.com)
  • Since IKBKG helps activate NF-κB, which protects cells against TNF-alpha induced apoptosis, a lack of IKBKG (and hence a lack of active NF-κB) makes cells more prone to apoptosis. (wikipedia.org)
  • This prompted us to investigate whether stimulation of glutamate receptors can activate NF-kappa B, which is present in neurons in either inducible or constitutive form. (nih.gov)
  • TL1A and DR3 activate NF-κB in vascular endothelial cells, and can be an important regulator of renal interstitial vascular injury. (biomedcentral.com)
  • A mutated tax expression vector, which fails to activate NF kappa B, was unable to induce either murine or human c-myc-CAT or URE/IRE-TK-CAT constructs. (scripps.edu)
  • Point mutations of FLIP at cysteine residues 254 and 259 prevent FLIP S-nitrosylation and its ability to activate NF-kappa B. The mechanism by which FLIP nitrosylation regulates NF-kappa B activity involves RIP1 binding and redistribution, whereas TRAF2 binding and distribution are unaffected. (cdc.gov)
  • Immunofluorescent staining was used to show the nuclear translocation of nuclear factor kappa b (NF-kappaB) p65. (medscimonit.com)
  • Because adjacent binding sites for the inducible transcription factors NF-kappa B and NF-IL-6 are located within this region, we examined the functional interaction of these two transcription factor families in IL-8 gene regulation. (jimmunol.org)
  • Conclusion: Our results indicate that normal carbohydrate concentrations also are able to regulate NF-κB transcription factors suggesting that these substances may play a role in ovarian angiogenesis. (endocrine-abstracts.org)
  • Regulation of human immunodeficiency virus type 1 and cytokine gene expression in myeloid cells by NF-kappa B/Rel transcription factors. (asm.org)
  • Enhancement of HIV-1 replication is related in part to increased DNA-binding activity of cellular transcription factors such as NF-kappa B. NF-kappa B binds to the HIV-1 enhancer region of the long terminal repeat and contributes to the inducibility of HIV-1 gene expression in response to multiple activating agents. (asm.org)
  • DNMT3L interacts with transcription factors to target DNMT3L/DNMT3B to specific DNA sequences: role of the DNMT3L/DNMT3B/p65-NFκB complex in the (de-)methylation of TRAF1. (semanticscholar.org)
  • Understanding the function of transcription factors, such as nuclear factor kappa?B (NF-kappa B), in acute liver injury may provide some answers to the molecular mechanisms of toxic insults. (elsevier.com)
  • Coexpression nfkappa brel and sp1 transcription factors human immunodeficiency virus 1induced. (informe.com)
  • Expression of tax activates several cellular transcription factors, including NF kappa B. We have previously identified two functional NF kappa B binding sites within the murine c-myc gene: upstream regulatory element (URE) and internal regulatory element (IRE). (scripps.edu)
  • However, IL-2 induction also produced an increase in mRNA for NF-kappa B p105, indicating an additional pretranslational component of regulation. (jimmunol.org)
  • Anti-mastitis SNV identification of NFκB1 in Chinese Holstein cows and the possible anti-inflammation role of NFκB1/p105 in bovine MECs. (wroc.pl)
  • NF-kappa B is a transcription factor involved in the regulation of the HIV long terminal repeat and is selectively activated following HIV infection of human macrophages. (asm.org)
  • Finally, we demonstrate that I kappa B alpha is rapidly resynthesized after loss, indicating that an autoregulatory mechanism is involved in the regulation of NF-kappa B function. (asm.org)
  • We believe that these results may highlight the importance of NF-κB regulation as well as the clinical potency of DHMEQ in the treatment of metastatic bladder cancer. (biomedcentral.com)
  • A New Paradigm to Mitigate Osteosarcoma by Regulation of MicroRNAs and Suppression of the NF-κB Signaling Cascade. (uni-bielefeld.de)
  • Regulation human immunodeficiency virus type and cytokine gene expression myeloid cells nfkappa brel. (informe.com)
  • The transcription factor nfkb kappa nfkb nuclear factor widely studied due its implication the regulation of. (informe.com)
  • Regulates the expression of IL-2, IL-6, and other cytokines through regulation on NF-kappa-B activity. (rcsb.org)
  • Cloning and functional analysis of the STAT-4 promoter showed that a NF-kappaB binding site, localized at -969/-959 bp upstream of the transcriptional start site, is involved in the regulation of this gene in primary human DC. (archives-ouvertes.fr)
  • Sun SC, Ley SC (2008) New insights into NF-κB regulation and function. (springer.com)
  • In this study, we provide new evidence for the regulation of NF-kappa B by FLIP through S-nitrosylation, which involves covalent modification of the protein's cysteine thiol by nitric oxide to form S-nitrosothiol. (cdc.gov)
  • NFκB is a transcription factor, which when activated is transported from the cytoplasm to the nucleus in cells exposed to mitogens or growth factors. (scbt.com)
  • Activated NFKB complex translocates into the nucleus and binds DNA at kappa-B-binding motifs such as 5-prime GGGRNNYYCC 3-prime or 5-prime HGGARNYYCC 3-prime (where H is A, C, or T, R is an A or G purine, and Y is a C or T pyrimidine). (biomol.com)
  • However, the unphosphorylated form resynthesized after cell stimulation is able to bind NF-kappa-B allowing its transport to the nucleus and protecting it to further NFKBIA -dependent inactivation. (sdsc.edu)
  • In this study, we examine the role of the dynein/dynactin motor complex in the cellular mechanism targeting and transporting activated NF-kappa B to the nucleus in response to synaptic stimulation. (uni-bielefeld.de)
  • This study shows the molecular mechanism for the retrograde transport of activated NF-kappa B from distant synaptic sites towards the nucleus. (uni-bielefeld.de)
  • Nevertheless, the HDAC-NF-kappa B interactions in inflammatory signalling have not been fully understood. (rug.nl)
  • Life Extension Foundation have an article on NF-Kappab in their November magazine entitled "The Inflammatory Factor Underlying Most Cancers. (healthblogs.org)
  • [email protected] Autorzy nie zgłaszają konfliktu interesu Abstract The Nuclear Factor kappa B (NF-κB) plays a crucial role in immune and inflammatory processes. (studylibpl.com)
  • We provided evidence that inflammaging may involve a novel link between the effects of ICA on SIRT6 (a regulator of aging) and NF- κ B (a regulator of inflammation). (hindawi.com)
  • This review focuses on the role of HDAC 3 in (NF-kappa B-mediated) inflammation and NF-kappa B lysine acetylation. (rug.nl)
  • ESE-1 is a novel transcriptional mediator of inflammation that interacts with NF-kappa B to regulate the inducible nitric-oxide synthase gene. (harvard.edu)
  • While NF-κB inhibitory drugs have previously been attractive to disease such as chronic inflammation and diabetes, specific cancers have been shown to have constitutive NF-κB activity. (wikipedia.org)
  • These results suggest that tax can transactivate the c-myc gene through NF kappa B. The tax-induced stimulation of this oncogene may play a role in T cell immortalization. (scripps.edu)
  • The stimulation of Akt is, however, detected only after I kappa B-alpha degradation is induced by these agents. (elsevier.com)
  • Co-transfection of a super repressor I-kappa B-alpha vector completely abrogated the stimulation with 50 micromolar Fe 2+ (Figure 1 ). (biomedcentral.com)
  • Evidence is presented for a direct interaction between GR and the NF-kappa B subunits p65 and p50. (asm.org)
  • The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA. (ucdenver.edu)
  • In Pam3CSK4 treated cells, active NF-κB subunits p50 and p65 increased in cell nuclear fractions as early as 1.5 h. (biomedcentral.com)
  • The levels of the p65, p52, and RelB subunits of NF-kB and IkB-α were determined by western blot analysis and ELISA. (biomedcentral.com)
  • Urban MB, Baeuerle PA (1991) The role of the p50 and p65 subunits of NF-kappa B in the recognition of cognate sequences. (springer.com)
  • In addition, NF-kappa B p65 (RelA), but not NF-kappa B p50 (NFKB1), binds specifically to the NF-kappa B site. (jimmunol.org)
  • NF-Kappa-B antibody LS-C9278 is an unconjugated rabbit polyclonal antibody to human NF-Kappa-B (NFKB1). (lsbio.com)
  • NF-kappa-B is composed of NFKB1 or NFKB2 bound to either REL, RELA, or RELB. (gentaur.se)
  • The most abundant form of NF-kappa-B is NFKB1 complexed with the product of this gene, RELA. (gentaur.se)
  • this binding is dependent on intact binding sites for both NF-IL-6 and RelA. (jimmunol.org)
  • Do jednej grupy należą białka: RelA, RelB i cRel, natomiast do drugiej białka: NF-κB1 oraz NF-κB2 [3, 5-7]. (studylibpl.com)
  • Molecular sequence data nfkappa the nuclear factorkappa rela transcription factor constitutively activated human pancreatic adenocarcinoma cells. (informe.com)
  • O papel do fator nuclear kappa B (NF-kB) e do eixo IL-12/23-IFN-g na ativação do. (usp.br)
  • Thus, here, we tested whether the ubiquitous transcription factor NF-κB, which regulates myogenic differentiation and is also a promising therapeutic target in the treatment of other types of tumors, might be an interesting candidate for the development of novel rhabdomyosarcoma treatment strategies. (biomedsearch.com)
  • Short-term treatment with 0.1-5 muM As(III) up-regulates expression of c-Fos and c-Jun and the redox regulators, thioredoxin (Trx) and Redox factor-1 (Ref-1) and activates both AP-1 and NF-kappaB binding. (edu.au)
  • DDRGK1 regulates NF-?B activity by modulating I?B? (nih.gov)
  • NF-kappa B is a widely used regulator of inducible and tissue-specific gene control. (pnas.org)
  • Differential interactions relnfkappa complexes with kappa alpha determine pools constitutive and inducible nfkappa activity. (informe.com)
  • We show that after the induction of differentiation, NF-κB activity declines rapidly in normal myoblasts, but only slightly in rhabdomyosarcoma cells. (biomedsearch.com)
  • This report demonstrates that Heat killed probiotic bacteria, L.plantarum can stimulate the immune cells by induction of NF -κB. (ijpbs.net)
  • fig-1: Induction of NF-kB activity by LPS in NF-kB Leeporter™ - RAW264.7 cells. (abeomics.com)
  • Modulation of transcription factor NF-kappa B binding activity by oxidation-reduction in vitro. (pnas.org)
  • In addition, we inhibited NF-κB activity in these cells and analyzed the effects on myogenic differentiation. (biomedsearch.com)
  • The study revealed that the exposure of MM6 cells to 56Fe ions resulted in increased NF-kappa B DNA-binding activity. (biomedsearch.com)
  • We started with the premise that NF-kappa B activity might be helpful in protecting cells against the harmful effects of radiation," Dr. Rodeck said. (medicalxpress.com)
  • These data reveal a second mechanism by which NF-kappa B activity may be regulated by DEX. (asm.org)
  • Surprisingly, while both AP-1 and NF-kappa B can be inhibited by activated GR, synergistic NF-kappa B/AP-1 activity is largely unaffected. (asm.org)
  • Chronic HIV-1 infection of myeloid cells leads to constitutive NF-kappa B DNA-binding activity and provides an intranuclear environment capable of perpetuating HIV-1 replication. (asm.org)
  • Interestingly, we demonstrate Gli-stimulated IKBKE (IKK\(\varepsilon\))/nuclear factor-\(\kappa\)B (NF-\(\kappa\)B) activity in pancreatic cancer cells in culture and in vivo, and show that this activity is a critical downstream mediator for Gli-dependent PDAC cell transformation and survival. (harvard.edu)
  • These results suggest that As(III) may alter AP-1 and NF-KB activity, in part, by up-regulating Trx and Ref-1. (edu.au)
  • DNA-binding activity of NF-κB was detected by electrophoretic mobility shift assay. (biomedcentral.com)
  • NF-κB activity was evaluated through a secretory alkaline phosphatase reporter assay (SEAP). (biomedcentral.com)
  • NF-κB activity in HCE-T cells treated with TLR2 activator Pam3CSK4 was higher than control cells at both 6 and 24 h. (biomedcentral.com)
  • Reports in the literature concerning the systemic response to, and the effect of, common breast cancer therapy on NF-kappa B and antioxidative defence enzyme expression and activity under clinical conditions are scarce. (ac.rs)
  • Therefore, downregulating NF-κB activity is an important goal of cancer treatment. (ch3biosystems.com)
  • Note DN-I-kappa B completely blocks iron induced promoter activity. (biomedcentral.com)
  • Advanced B-cell lymphoma (ABC), a subtype of Diffuse large B-cell lymphoma (DLBCL) has been shown to have fundamental and upregulated NF-κB activity. (wikipedia.org)
  • Notably, aberrant NF-κB activity is strongly associated with many aspects of the pathology of rheumatoid arthritis. (wikipedia.org)
  • Furthermore, using DNA templates containing two copies of the PRDII domain linked to the rabbit beta globin gene, the purified polypeptides specifically stimulated NF-kappa B dependent transcription in an in vitro reconstitution assay as heterodimers but not as p50 homodimers. (nih.gov)
  • We now demonstrate that NF-kappa B binding in vitro can be inhibited by agents that modify free sulfhydryls. (pnas.org)
  • Finally, an increase in the ratio of oxidized to reduced glutathione was shown to inhibit NF kappa B-DNA binding in vitro. (tcd.ie)
  • In this line, we show that p65 is associated with components of the dynein/dynactin complex in vivo and in vitro and that the nuclear localization sequence (NLS) within NF-kappa B p65 is essential for this binding. (uni-bielefeld.de)
  • Fingerprint Dive into the research topics of 'Akt is a downstream target of NF-kappa B.'. Together they form a unique fingerprint. (elsevier.com)
  • Increased intracellular stores of latent NF-kappa B may also result in rapid inducibility of NF-kappa B-dependent cytokine gene expression. (asm.org)
  • Das IKBKG-gen kodiert ein Modulator der NF-kappa-B-Funktion. (moldiag.com)
  • Isolation of full-length cDNA and chromosomal localization of human NF-kappaB modulator NEMO to Xq28. (moldiag.com)
  • In the cytosol, when complexed to an inhibitory molecule, I kappa B, NF-kappa B is in an inactive form and cannot bind DNA. (pnas.org)
  • Gene deletion studies have shown that receptor activator of NF-kappaB ligand (RANKL) is one of the critical mediators of osteoclastogenesis. (greenmedinfo.com)
  • View detailed NF kappa B Activator specifications, including NF kappa B Activator CAS number, molecular weight, molecular formula and chemical structure, by clicking on the product name. (scbt.com)
  • the attention have been recently placed on the receptor of activator of NF(Kappa)B ligand receptor (RANKL) and osteoprotegerin (OPG), namely RANKL/OPG system. (minervamedica.it)
  • To further improve their immunogenicity, the DCs were additionally activated by co-transfection with the constitutively active nuclear factor (NF)-κB activator caIKK. (dtu.dk)
  • NFkB was identified as a sequence specific transcriptional activator that binds to the intronic enhancer of kappa light chain gene in B lymphocytes. (biomol.com)
  • Current mathematical modeling frameworks for NF-$\kappa $B signal transduction, though limited to a small signaling module located in a downstream of IKK, heavily rely on the parameterizations and the numerical studies of ODE models and doubtless lack intuitive explanations about underlying mechanisms of the dynamic patterns of the NF-$\kappa $B signaling. (aps.org)
  • Akt is a downstream target of NF-kappa B. (elsevier.com)
  • Akt is a downstream target of NF-kappa B. The Journal of biological chemistry , 277 (33), 29674-29680. (elsevier.com)
  • Meng F , Liu L , Chin PC, D'Mello SR. Akt is a downstream target of NF-kappa B. The Journal of biological chemistry . (elsevier.com)
  • 000114841 001__ 114841 000114841 005__ 20181203021031.0 000114841 037__ $$aARTICLE 000114841 245__ $$aCharacterization of a new tissue-specific transcription factor binding to the simian virus 40 enhancer TC-II (NF-kappa B) element 000114841 269__ $$a1992 000114841 260__ $$c1992 000114841 336__ $$aJournal Articles 000114841 500__ $$aSwiss Institute for Experimental Cancer Research, Epalinges. (epfl.ch)
  • Further, conditioned medium derived from NF-κB activated LNCaP cells induce osteoclast differentiation. (ox.ac.uk)
  • Santa Cruz Biotechnology now offers a broad range of NF kappa B Activators. (scbt.com)
  • The transcription factor nuclear factor (NF)-kappaB has been suggested to be a key mediator of the development of lymph nodes and Peyer's patches. (caltech.edu)
  • Because of this extensive role in immune action, NF- kB has been termed the central mediator of the immune response. (lymerick.net)
  • It is therefore possible that modulation of the redox state of NF-kappa B could represent a post-translational control mechanism for this factor. (pnas.org)
  • Afterwards, the amount of NF-κB factors (cRel, RelB, p50, p52, p65) was quantified by ELISA and compared between stimulated and control cells. (endocrine-abstracts.org)
  • Gentaur's NF-?B p65 ELISA kit utilizes the Sandwich-ELISA principle. (gentaur.se)
  • The micro ELISA plate provided in this kit has been pre-coated with an antibody specific to Mouse NF-?B p65. (gentaur.se)
  • Post-translational modification of I-kappa B alpha activates NF-kappa B in human monocytes exposed to 56Fe ions. (biomedsearch.com)
  • The objective of this study was to investigate whether heavy ion (56Fe) radiation exposure activates one of the key transcriptional regulators, nuclear factor-kappa B (NF-kappa B), in normal human monocytes (Mono Mac 6 cells: MM6). (biomedsearch.com)
  • Here we present a systematic way to derive a minimal model from an up-to-dated and detailed NF-$\kappa $B signaling network by means of sensitivity analysis. (aps.org)
  • ET-1 administration slightly downregulated gene expression of p65 of NF- κ B but potently and in a dose-dependent way downregulated p21-cip gene expression in the liver. (hindawi.com)
  • In contrast, IL-2 exerts only minor effects on NF-kappa B p65 mRNA expression. (jimmunol.org)
  • These data suggest that NF-kappa B, AP-1, and GR interact in a complex regulatory network to modulate gene expression and that cross-coupling of NF-kappa B and GR plays an important role in glucocorticoid-mediated repression of cytokine transcription. (asm.org)
  • Also, few studies have described the changes in NF-κB expression in such tumors. (biomedcentral.com)
  • On the other hand, NF-κB-mediated expression of anti-microbial molecules human defensin (hBD)-2 and homeostatic molecules manganese superoxide dismutase may help to control the pathogenicity of microbes or increase defences against oxidative stress [ 15 , 18 ]. (biomedcentral.com)
  • NF-{kappa}B is required for STAT-4 expression during dendritic cell maturation. (archives-ouvertes.fr)
  • In addition, we studied whether this would be followed by upregulation of the NF-kappa B target gene product granulocyte-macrophage colony-stimulating factor (GM-CSF). (ersjournals.com)
  • In class I and class II MHC-restricted TCR transgenic mice, transcription of I kappa BNS is stimulated by peptides that trigger negative selection but not by those inducing positive selection (i.e., survival) or nonselecting peptides. (ucm.es)
  • Since NF-κB is essential to CLL cells survival it is suggested that NF-κB could be a new therapeutic target in CLL. (studylibpl.com)
  • Description: Description of target: NF-kappa-B is a ubiquitous transcription factor involved in several biological processes. (gentaur.se)
  • However, in most cancers, NF-κB is abnormally activated constitutively, contributing thus to oncogenesis and tumor progression. (ch3biosystems.com)