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Carbamates in which the -CO- group has been replaced by a -CS- group.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): ...
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 ... In the case of NF-κB, the C-terminal dimerization subdomain determines dimerization propensity with other proteins in the NF-κB ... The Rel homology domain (RHD) is a protein domain found in a family of eukaryotic transcription factors, including both NF-κB ... Biancalana M, Natan E, Lenardo MJ, Fersht AR (September 2021). "NF-κB Rel subunit exchange on a physiological timescale". ...
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. ...
Curcumin's mechanism of action is anti-inflammatory; it inhibits the nuclear transcriptional activator kappa B (NF-KB) that is ... Demarchi F, Bertoli C, Sandy P, Schneider C (October 2003). "Glycogen synthase kinase-3 beta regulates NF-kappa B1/p105 ... GSK-3 is also involved in nuclear transcriptional activator kappa B (NFκB) signaling pathway, Hedgehog signaling pathway, Notch ... GSK-3 also seems to be responsible for NFκB aberrant activity in pediatric acute lymphoblastic leukemia and pancreatic cancer ...
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 ...
1 July 2005). "Macrophages induce invasiveness of epithelial cancer cells via NF-kappa B and JNK". Journal of Immunology. 175 ( ... on epithelial tumor cells in human ovarian cancer Macrophages induce invasiveness of epithelial cancer cells via NF-kappa B and ...
"ABIN-2 forms a ternary complex with TPL-2 and NF-kappa B1 p105 and is essential for TPL-2 protein stability". Molecular and ... "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology. 6 (2): 97- ... "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology. 6 (2): 97- ... "Akt-dependent phosphorylation specifically regulates Cot induction of NF-kappa B-dependent transcription". Molecular and ...
"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. ... Schmidt N, Kowald L, Wijk S, Fulda S (2019). "Differential involvement of TAK1, RIPK1 and NF-kappaB signaling in Smac mimetic- ... pathogen Salmonella Typhimurium as the local NF-κB signalling platform and provided insights into the function of OTULIN in NF- ... "Specific recognition of linear ubiquitin chains by NEMO is important for NF-κB activation". Cell. 136 (6): 1098-1109. doi: ...
"The activity of hsp90 alpha promoter is regulated by NF-kappa B transcription factors". Oncogene. 27 (8): 1175-8. doi:10.1038/ ... NF-κB or RELA also induces HSP90AA1 expression possibly explaining the pro-survival ability of NF-κB-driven transcription. ... Hu Y, Mivechi NF (May 2003). "HSF-1 interacts with Ral-binding protein 1 in a stress-responsive, multiprotein complex with ... Bohonowych JE, Hance MW, Nolan KD, Defee M, Parsons CH, Isaacs JS (Apr 2014). "Extracellular Hsp90 mediates an NF-κB dependent ...
"Substance P induces TNF-alpha and IL-6 production through NF kappa B in peritoneal mast cells". Biochimica et Biophysica Acta ( ... Data suggest that nuclear translocation of NF-κB regulates IL-6 overexpression in SP-stimulated cells.[90] This is of key ... It appears that unlike IL-6 signalling in macrophages, which is dependent upon activation of the NFκB signalling pathway, ... whereas IL-6 activation and signalling in muscle is totally independent of a preceding TNF-response or NFκB activation, and is ...
2003). "Direct binding of Toll-like receptor 2 to zymosan, and zymosan-induced NF-kappa B activation and TNF-alpha secretion ...
Karin, M; Delhase, M (2000). "The I kappa B kinase (IKK) and NF-kappa B: Key elements of proinflammatory signalling". Seminars ... 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, ... This activity is usually attributed to the role of proteasomes in the activation of NF-κB which further regulates the ...
... oxidase 4 isozyme is essential for lipopolysaccharide-induced production of reactive oxygen species and activation of NF-kappa ...
"A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology. 6 (2): 97- ...
N-arachidonoyl-dopamine inhibits activation of the NF-kappa B, NFAT, and activator protein 1 signaling pathways". 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 ... Leung TH, Zhang LF, Wang J, Ning S, Knox SJ, Kim SK (December 2013). "Topical hypochlorite ameliorates NF-κB-mediated skin ...
Chen BC, Wu WT, Ho FM, Lin WW (July 2002). "Inhibition of interleukin-1beta -induced NF-kappa B activation by calcium/ ... "The Fas-associated death domain protein suppresses activation of NF-kappa B by LPS and IL-1 beta". The Journal of Clinical ... "Murine TOLL-like receptor 4 confers lipopolysaccharide responsiveness as determined by activation of NF kappa B and expression ... "Murine TOLL-like receptor 4 confers lipopolysaccharide responsiveness as determined by activation of NF kappa B and expression ...
2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97 ...
Hsu H, Xiong J, Goeddel DV (June 1995). "The TNF receptor 1-associated protein TRADD signals cell death and 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. ... "Critical roles of TRAF2 and TRAF5 in tumor necrosis factor-induced NF-kappa B activation and protection from cell death". J. ... Sanz L, Sanchez P, Lallena MJ, Diaz-Meco MT, Moscat J (1999). "The interaction of p62 with RIP links the atypical PKCs to NF- ...
"Physical association and functional antagonism between the p65 subunit of transcription factor NF-kappa B and the ... GR transrepression via NF-κB and AP-1 is restricted only to certain cell types, and is not considered the universal mechanism ... other transcription factors such as NF-κB or AP-1 themselves are able to transactivate target genes. However activated GR can ... "I kappaB alpha-independent downregulation of NF-kappaB activity by glucocorticoid receptor". The EMBO Journal. 16 (15): 4698- ...
Karin M, Delhase M (Feb 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, ... This activity is usually attributed to the role of proteasomes in the activation of NF-κB which further regulates the ...
The light chain of the monoclonal protein is usually the kappa light chain. At times, patients with Waldenström ... cytochrome c release NF-κB WNT/beta-catenin mTOR ERK MAPK Bcl-2 The protein Src tyrosine kinase is overexpressed in Waldenström ... usually of the kappa type, are found in the urine. Urine collections should be concentrated. Bence Jones proteinuria is ... and NF-κB pathways.[citation needed] In Waldenström macroglobulinemia cells, histone deacetylases and histone-modifying genes ...
Rosette C, Karin M (March 1995). "Cytoskeletal control of gene expression: depolymerization of microtubules activates NF-kappa ...
Zinc inhibits NF-κB pathways, is antiproliferative, and induces apoptosis in abnormal cells. Unfortunately, oral ingestion of ... Uzzo RG, Leavis P, Hatch W, Gabai VL, Dulin N, Zvartau N, Kolenko VM (November 2002). "Zinc inhibits nuclear factor-kappa B ...
NF-kappa B - nicotinic receptor - nitrogen - nitroglycerine - Nobel Prize in Chemistry - non-competitive inhibition - nuclear ... kappa opioid receptor - kappa-chain immunoglobulin - karyoplasm - karyotype - kelvin - keratin - kinase - kinesin - kinetic ...
2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97 ...
2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97 ...
Molnár K, Vannay A, Szebeni B, Bánki NF, Sziksz E, Cseh A, Győrffy H, Lakatos PL, Papp M, Arató A, Veres G (July 2012). " ... doi:10.1007/978-1-4613-2970-1_9. ISBN 978-1-4613-2972-5. Mueller MN, Kappas A (October 1964). "Estrogen pharmacology. I. The ...
... with downregulated cardiac myocyte levels further dependent upon NF-kappa B. MicroRNA Ralfkiaer U, Hagedorn PH, Bangsgaard N, ...
"A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97-105. ... "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97-105. ... Kanayama A, Seth RB, Sun L, Ea CK, Hong M, Shaito A, Chiu YH, Deng L, Chen ZJ (2004). "TAB2 and TAB3 activate the NF-kappaB ... Ma Q, Zhou L, Shi H, Huo K (Jun 2008). "NUMBL interacts with TAB2 and inhibits TNFalpha and IL-1beta-induced NF-kappaB ...
IRF3 cooperative activation with NF-κB transcription factor through phosphorylation leads to the induction of the IFNβ promoter ... and the SNX8 acts as an adaptor or scaffolding protein by permitting the recruitment of the inhibitor of nuclear factor-kappa-B ...
NF-kappa B and AP-1, three nuclear factors regulating interleukin-2 gene enhancer activity". European Journal of Immunology. 24 ... "Isolation of two new members of the NF-AT gene family and functional characterization of the NF-AT proteins". Immunity. 2 (5): ... Crabtree GR (Mar 1999). "Generic signals and specific outcomes: signaling through Ca2+, calcineurin, and NF-AT". Cell. 96 (5): ... of HIV gp120 and anti-CD4 antibodies with the CD4 molecule on human CD4+ T cells inhibits the binding activity of NF-AT, ...
ORF2 is thought to either encode a protein with phosphatase activity (TTMVs) or a peptide that suppresses the NF- κ {\ ... displaystyle \kappa } B pathways (TTVs). It was seen to have a highly conserved motif in the N-terminal part. Anellovirus ... Torque teno virus (SANBAN Isolate) ORF2 protein suppresses NF-κB pathways via interaction with IκB kinases. Journal of virology ...
In the arteries of the brain, high levels of calcium in mitochondria elevates activity of nuclear factor kappa B NF-κB and ...
"Interaction of TAFII105 with selected p65/RelA dimers is associated with activation of subset of NF-kappa B genes". J. Biol. ... Yamit-Hezi A, Dikstein R (1998). "TAFII105 mediates activation of anti-apoptotic genes by NF-kappaB". EMBO J. 17 (17): 5161-9. ... "TAFII105 mediates activation of anti-apoptotic genes by NF-kappaB". EMBO J. 17 (17): 5161-9. doi:10.1093/emboj/17.17.5161. PMC ...
2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97 ...
2002). "A novel PAAD-containing protein that modulates NF-kappa B induction by cytokines tumor necrosis factor-alpha and ... a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing ... 2002). "Functional screening of five PYPAF family members identifies PYPAF5 as a novel regulator of NF-kappaB and caspase-1". ...
When all three BAFF receptors are stimulated, levels of NF kappa B, which contributes to cell proliferation and differentiation ...
This process is mediated by the NF-κB (nuclear factor-kappa B) complex, a ubiquitous transcription factor involved in cellular ...
I-KAPPA-B-ALPHA/NF-KAPPA-B COMPLEX ... I-KAPPA-B-ALPHA/NF-KAPPA-B COMPLEX. *PDB DOI: 10.2210/pdb1NFI/ ... NF-KAPPA-B P65. A, C. 301. Homo sapiens. Mutation(s): 0 Gene Names: RELA, NFKB3. ... NF-KAPPA-B P50. B, D. 107. Homo sapiens. Mutation(s): 0 Gene Names: NFKB1. ... I-KAPPA-B-ALPHA. E, F. 213. Homo sapiens. Mutation(s): 0 Gene Names: NFKBIA, IKBA, MAD3, NFKBI. ...
... Am J Physiol Lung ... NF-kappaB binding was assessed using the electromobility shift assay, and activity was measured using a luciferase reporter ... Pretreatment with omega-3 FA inhibited IkappaB phosphorylation and significantly decreased NF-kappaB activity. Moreover, omega- ... through inactivation of the NF-kappaB signal transduction pathway secondary to inhibition of IkappaB phosphorylation. ...
Resorcylic Acid Lactones with Cytotoxic and NF-kappa B Inhibitory Activities and Their Structure-Activity Relationships. ... Resorcylic Acid Lactones with Cytotoxic and NF-kappa B Inhibitory Activities and Their Structure-Activity Relationships ... 2011). Resorcylic Acid Lactones with Cytotoxic and NF-kappa B Inhibitory Activities and Their Structure-Activity Relationships ... and NF-kappa B. In the latter assay, compounds 1 and S displayed sub-micromolar activities that were on par with the positive ...
A component of NF-kappa B transcription factor. It is proteolytically processed from NF-kappa B p105 precursor protein and is ... NF-kappa B p105 Precursor Protein*NF-kappa B p105 Precursor Protein ... "NF-kappa B p50 Subunit" by people in this website by year, and whether "NF-kappa B p50 Subunit" was a major or minor topic of ... "NF-kappa B p50 Subunit" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical ...
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 - Mus musculus (house mouse) [ 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- ...
NF-kappa-B interacting protein 1. Next entry:. NF-kappa-B subunit 2. Random entry:. heterogeneous ribonucleoprotein A18. ... NF-kappa-B subunit 1. see: NF-kappa-B.. ... ... ... ... ... Subscribe to continue reading! ... .... ...
Elevated TLR5 expression in vivo and loss of NF-kappa B activation via TLR5 in vitro detected in HPV-negative oropharyngeal ... Elevated TLR5 expression in vivo and loss of NF-kappa B activation via TLR5 in vitro detected in HPV-negative oropharyngeal ... TLRs control innate immune responses by activating, among others, the nuclear factor-κΒ (NF-κΒ) signaling pathway. Elevated NF- ... Elevated TLR5 expression in vivo and loss of NF-kappa B activation via TLR5 in vitro detected in HPV-negative oropharyngeal ...
... nuclear factor kappa B (NF- [kappa]B), and tumor necrosis factor [alpha] (TNF-[alpha]) gene expressions, and interleukin-18 (IL ... Taurine alleviates kidney injury in a thioacetamide rat model by mediating Nrf2/HO-1, NQO-1, and MAPK/NF-[kappa]B signaling ... du NF-[kappa]B et du TNF[alpha], de meme que des taux en proteines dIL-18 et de TNF[alpha] par rapport aux rats dont les reins ... la taurine exerce son effet antiinflammatoire par lintermediaire de la regulation de la transcription du NF-[kappa]B et de la ...
NF-κB has also been proposed to be required for p53-induced apoptosis in transformed cells. However, the involvement of NF-κB ... Here we show that p73 is activated after genotoxin treatment only in the presence of NF-κB and that p73 induces Noxa gene ... Here we investigate this mechanism and show that in transformed MEFs lacking NF-κB (p65-null cells) genotoxin-induced ... Moreover, we find that in the absence of NF-κB, genotoxin treatment cannot induce Noxa mRNA expression. Noxa expression had ...
Ginsenoside Rg1 alleviates acute liver injury through the induction of autophagy and suppressing NF-kappa B/NLRP3 inflammasome ... Ginsenoside Rg1 alleviates acute liver injury through the induction of autophagy and suppressing NF-kappa B/NLRP3 inflammasome ... Ginsenoside Rg1 alleviates acute liver injury through the induction of autophagy and suppressing NF-kappa B/NLRP3 inflammasome ...
NF-κB) protein complex. NF-κB is a transcription factor that is activated by various intra- and extra-cellular stimuli such as ... Activated NF-κB translocates into the nucleus and stimulates the expression of genes involved in a wide variety of biological ... The 105 kD protein is a Rel protein-specific transcription inhibitor and the 50 kD protein is a DNA binding subunit of the NF- ... Nuclear factor NF-kappa-B p105 subunit isa 105 kD protein which can undergo cotranslational processing by the 26S proteasome to ...
Insights into the Relationship between Nucleolar Stress and the NF-kappa B Pathway. Chen, J. & Stark, L. A., Oct 2019, In: ... IDENTIFICATION OF NUCLEAR PATHWAYS THAT ARE CASUALLY INVOLVED IN NUCLEAR TARGETING OF NF-KAPPA B /RELA. *Stark, Lesley ( ... Crosstalk between NF-KB and Nucleoli in the Regulation of Cellular Homeostasis: NF- kappaB nucleoli crosstalk in stress ... and the ubiquitylation and nucleolar translocation of the RelA NF-kappa B subunit. OHara, A., Simpson, J., Morin, P., ...
NF-κB p100/p52(Phospho-Ser865)Antibody 50μg. 218,50 WB; IHC. ... NF-κB p65(Ab-254)Antibody. 50μg. 160,00 IHC. 21010-2. 100μg. ... NF-κB p100/p52(Phospho-Ser869)Antibody 50μg. 218,50 WB; IHC. ... NF-κB p65(Phospho-Ser468)Antibody. 50μg. 218,50 WB. 11013-2. ... NF-κB p105/p50(Phospho-Ser337)Antibody 50μg. 218,50 WB; IHC. ... NF-κB p105/p50(Phospho-Ser893)Antibody 50μg. 218,50 WB; IHC. ... NF-κB p105/p50(Phospho-Ser907)Antibody 50μg. 218,50 WB; IHC. ... NF-κB p105/p50(Phospho-Ser932)Antibody 50μg. 218,50 WB; IHC. ...
A treatment with 5%(v/v) coffee extract and more than 2.5 μM pyrocatechol inhibited the LPS-induced activation of NF-κB and ... Mutual regulation of the transcriptional activator NF-kappa B and its inhibitor, I kappa B-alpha. Proc. Natl Acad. Sci. USA 90 ... Sun, S. C., Ganchi, P. A., Ballard, D. W. & Greene, W. C. NF-kappa B controls expression of inhibitor I kappa B alpha: evidence ... NF-kappa B and Sp1 regulate transcription of the human monocyte chemoattractant protein-1 gene. J. Immunol. 153, 2052-2063 ( ...
A mutation in Nischarin causes otitis media via LIMK1 and NF-kappaB pathways. View publications ...
17-Aminogeldanamycin Inhibits Constitutive Nuclear Factor-Kappa B (NF-κB) Activity in Patient-Derived Melanoma Cell Lines ... Role of Nuclear factor kappa B (NF-κB) Signalling in Neurodegenerative Diseases: An Mechanistic Approach. ... 17-Aminogeldanamycin Inhibits Constitutive Nuclear Factor-Kappa B (NF-κB) Activity in Patient-Derived Melanoma Cell Lines ... 17-Aminogeldanamycin Inhibits Constitutive Nuclear Factor-Kappa B (NF-κB) Activity in Patient-Derived Melanoma Cell Lines ...
CYP = cytochrome P; IL = interleukin; NF-κB = nuclear factor-kappa B; ROS = reactive oxygen species; TNF = tumor necrosis ...
The TNFRSF11A gene provides instructions for making a protein called receptor activator of NF-κB (RANK). Learn about this gene ... receptor activator of NF-kappa-B. *receptor activator of nuclear factor-kappa B ... The TNFRSF11A gene provides instructions for making a protein called receptor activator of NF-κB (RANK). This protein plays an ...
Combined inhibition of Bcl-2 and NFκB synergistically induces cell death in cutaneous T-cell lymphoma. Blood. 2019 Aug 1. 134 ( ... and Phi Beta Kappa ...
We conclude that NF-kappa B activation could constitute one of the mechanisms whereby the expression of kappa B-responsive ... We conclude that NF-kappa B activation could constitute one of the mechanisms whereby the expression of kappa B-responsive ... the onset of NF-kappa B activation was paralleled by a decline in immunoreactive I kappa B-alpha protein levels, and the ... the onset of NF-kappa B activation was paralleled by a decline in immunoreactive I kappa B-alpha protein levels, and the ...
Keywords: Map kinase, ERK5, NF-kB, Apoptosis, Endometrial cancer, Anticancer drug, NF-KAPPA-B, REGULATED KINASE-5, BREAST- ... our results suggest that the ERK5-NEMO-NF-kappa B pathway mediates EC cell proliferation and survival. We propose the ERK5/NF- ... The ERK5/NF-kappa B signaling pathway targets endometrial cancer proliferation and survival ... Pharmacologic inhibition or ERK5 silencing impaired NF-kB pathway in EC cells and xenografts. Furthermore, we found a positive ...
... Author: Schmid, Evi; Nguyen Thi ... Serum- and Glucocorticoid-Inducible Kinase 1 Sensitive NF-kappa B Signaling in Dendritic Cells. DSpace Repository. Login ...
NF-kappa B and related proteins: Rel/dorsal homologies meet ankyrin-like repeats. scientific article published on April 1, 1992 ... NF-kappa B and related proteins: Rel/dorsal homologies meet ankyrin-like repeats (English) ...
I-KAPPA-B-ALPHA/NF-KAPPA-B COMPLEX. 1ot8. Structure of the Ankyrin Domain of the Drosophila Notch Receptor. ... IKAPPABALPHA/NF-KAPPAB COMPLEX. 1ixv. Crystal Structure Analysis of homolog of oncoprotein gankyrin, an interactor of Rb and ... It shows a stack of six IkappaBalpha ankyrin repeats facing the C-terminal domains of the NF-kappaB Rel homology regions. ... The position of the sixth ankyrin repeat shows that full-length IkappaBalpha will occlude the NF-kappaB DNA-binding cleft. The ...
Furthermore, inhibition or activation of the nuclear factor-kappa B (NF-κB) pathway resulted in marked variations in the levels ... Moreover, inhibition of the NF-κB pathway increased cell apoptosis, which was partially rescued by ectopic over-expression of ... It potentially contributes to leukemogenesis through the NF-κB pathway in pediatric ALL patients. ... CTCF, suggesting that CTCF may play a significant role in the anti-apoptotic pathway mediated by NF-κB. Our results indicate ...
18 Zinatizadeh MR, Schock B, Chalbatani GM, Zarandi PK, Jalali SA, Miri SR: The Nuclear Factor Kappa B (NF-kB) signaling in ... Published evidence also implicates NFκB in regulation of islet beta cell function in health and diabetes [19, 24-26].. NFκB is ... Background/Aims: We recently reported increased phosphorylation (at S536) of the p65 subunit of NFκB (Rel A) in pancreatic beta ... 21 Mitchell S, Vargas J, Hoffmann A: Signaling via the NFκB system. Wiley Interdiscip Rev Syst Biol Med 2016;8:227-241.. https ...
... kappa}B. Wild-type and mutant Tax capable of activating NF-{kappa}B, but not Tax mutant incapable of activating NF-{kappa}B, ... A Tax mutant that did not activate NF-{kappa}B failed to activate cyclin D1 and D2 promoters. Inhibitors of NF-{kappa}B ( ... dominant negative I{kappa}Bs mutants) suppressed Tax-dependent activation of cyclin D1 and D2 promoters, indicating that Tax- ...
NF-κB. nuclear factor kappa-light-chain-enhancer of activated B cells. ... NF-kB, nuclear factor kappa B; NLRP3, NLR family pyrin domain containing 3; PAMPs, pathogen-associated molecular patterns; ROS ... NF-kB, nuclear factor kappa B; NLRP3, NLR family pyrin domain containing 3; PAMPs, pathogen-associated molecular patterns; ROS ... leading to the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), which in turn ...
In contrast, in macrophages neither MyD88, Mal/TIRAP, nor I kappa B kinase 2 (IKK2) are required for NF-kappa B activation or ... We found that MyD88 and Mal/TIRAP are essential for LPS-induced I kappa B alpha phosphorylation, NF-kappa B activation, and ... These observations demonstrate for the first time the existence of 2 distinct pathways of LPS-induced NF-kappa B activation and ... NF)-kappa B inflammatory cytokines in sepsis remains unclear. Major candidates for that process are myeloid differentiation ...
  • These experiments demonstrate that a mechanism for proinflammatory cytokine inhibition in murine macrophages by omega-3 FA is mediated, in part, through inactivation of the NF-kappaB signal transduction pathway secondary to inhibition of IkappaB phosphorylation. (nih.gov)
  • 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)
  • TLRs control innate immune responses by activating, among others, the nuclear factor-κΒ (NF-κΒ) signaling pathway. (helsinki.fi)
  • Compound Porcine Cerebroside and Ganglioside Injection (CPCGI) Attenuates Sevoflurane-Induced Nerve Cell Injury by Regulating the Phosphorylation of p38 MAP Kinase (p38MAPK)/Nuclear Factor kappa B (NF-κB) Pathway. (nf-kappab.com)
  • Baicalin Inhibits Cell Proliferation and Inflammatory Cytokines Induced by Tumor Necrosis Factor α (TNF-α) in Human Immortalized Keratinocytes (HaCaT) Human Keratinocytes by Inhibiting the STAT3/Nuclear Factor kappa B (NF-κB) Signaling Pathway. (nf-kappab.com)
  • The ERK5/NF-kappa B signaling pathway ta. (yyu.edu.tr)
  • Pharmacologic inhibition or ERK5 silencing impaired NF-kB pathway in EC cells and xenografts. (yyu.edu.tr)
  • Together, our results suggest that the ERK5-NEMO-NF-kappa B pathway mediates EC cell proliferation and survival. (yyu.edu.tr)
  • Furthermore, inhibition or activation of the nuclear factor-kappa B (NF-κB) pathway resulted in marked variations in the levels of CTCF mRNA and protein in leukemic cells, indicating that CTCF may be involved downstream of the NF-κB pathway. (biomedcentral.com)
  • Moreover, inhibition of the NF-κB pathway increased cell apoptosis, which was partially rescued by ectopic over-expression of CTCF, suggesting that CTCF may play a significant role in the anti-apoptotic pathway mediated by NF-κB. (biomedcentral.com)
  • It potentially contributes to leukemogenesis through the NF-κB pathway in pediatric ALL patients. (biomedcentral.com)
  • We next explored the mechanistic basis of CTCF function, which revealed that inhibition of nuclear factor-kappa B (NF-κB) activity down-regulated CTCF expression, whereas activation of the NF-κB pathway restored CTCF expression. (biomedcentral.com)
  • We found that MyD88 and Mal/TIRAP are essential for LPS-induced I kappa B alpha phosphorylation, NF-kappa B activation, and interleukin 6 (IL-6) or IL-8 production in fibroblasts and endothelial cells in a pathway that also requires IKK2. (ox.ac.uk)
  • There are several pathways leading to NF-kappa B-activation. (kegg.jp)
  • Taurine alleviates kidney injury in a thioacetamide rat model by mediating Nrf2/HO-1, NQO-1, and MAPK/NF-[kappa]B signaling pathways. (gale.com)
  • Distinct pathways of LPS-induced NF-kappa B activation and cytokine production in human myeloid and nonmyeloid cells defined by selective utilization of MyD88 and Mal/TIRAP. (ox.ac.uk)
  • These observations demonstrate for the first time the existence of 2 distinct pathways of LPS-induced NF-kappa B activation and cytokine production in human myeloid and nonmyeloid cells defined by selective utilization of TLR4, MyD88, Mal/TIRAP, and IKK2, and reveal a layer of complexity not previously expected. (ox.ac.uk)
  • Regardless of the initial insult, the intense tubular necrosis activates innate immunity pathways, such as TLR4/NF-?B and the NLRP3/IL-1beta inflammasome. (usp.br)
  • In the present study, we investigated the behavior of the NLRP3 and NF-kB pathways in the progression of CKDinduced AKI to GT. (usp.br)
  • On Day 1, GT rats exhibited marked albuminuria and creatinine retention, changes in the Na+ and K+ excretion fraction, acute tubular necrosis (ATN) with increased renal abundance of KIM-1, glomerular lesions, interstitial inflammation and activation of the TLR4/NF-kB and NLRP3/IL-1k pathways. (usp.br)
  • Association between anti-tumour necrosis factor treatment response and genetic variants within the TLR and NF{kappa}B signalling pathways. (cdc.gov)
  • In addition, early after infection, M45 contributes to transient activation of NF-κB signalling, but later on it blocks NF-κB-activating pathways by interacting with RIP1, NF-κB essential modulator (NEMO) and DNA-dependent activator of IFN-regulatory factors (DAI). (com.hr)
  • NF-kappa B p50 Subunit" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (umassmed.edu)
  • This graph shows the total number of publications written about "NF-kappa B p50 Subunit" by people in this website by year, and whether "NF-kappa B p50 Subunit" was a major or minor topic of these publications. (umassmed.edu)
  • Below are the most recent publications written about "NF-kappa B p50 Subunit" by people in Profiles. (umassmed.edu)
  • Nuclear factor NF-kappa-B p105 subunit isa 105 kD protein which can undergo cotranslational processing by the 26S proteasome to produce a 50 kD protein. (abbkine.com)
  • The 105 kD protein is a Rel protein-specific transcription inhibitor and the 50 kD protein is a DNA binding subunit of the NF-kappaB (NF-κB) protein complex. (abbkine.com)
  • We recently reported increased phosphorylation (at S536) of the p65 subunit of NFκB (Rel A) in pancreatic beta (INS-1 832/13) cells following exposure to hyperglycemic (HG) conditions. (cellphysiolbiochem.com)
  • Besides IκB, the p65 subunit of NFκB is functionally regulated via phosphorylation at its critical S276 and S536 residues. (cellphysiolbiochem.com)
  • In vitro, in vitro, IKKα and IKKβ are two independent kinases of IκBα, a large multiprotein complex that catalyzes the phosphorylation of the inhibitory subunit of NF-κB. (semanticscholar.org)
  • Furthermore, curcumin decreased the level of the p65 subunit of NF‑κB binding to the promoter of the gene encoding uPA and MMP9, which suppressed transcriptional activation of uPA and MMP9. (spandidos-publications.com)
  • The lungs were sliced into 5 micrometer thick sections which were examined for p65, a protein subunit of NF-kB, using an immunofluorescence technique. (cdc.gov)
  • In addition, taurine exerts its anti-inflammatory effect via regulating NF-[kappa]B transcription and subsequent production of pro-inflammatory mediators via mitogen-activated protein kinase (MAPK) signaling regulation. (gale.com)
  • NFκB is localized, in its inactive state, in the cytosolic compartment as a p65/p50 heterodimer via complexation with IκB proteins. (cellphysiolbiochem.com)
  • Activation of NF-κB is initiated by the signal-induced degradation of IκB proteins, the most studied of which is IκBα. (spandidos-publications.com)
  • Pretreatment with omega-3 FA inhibited IkappaB phosphorylation and significantly decreased NF-kappaB activity. (nih.gov)
  • Under conditions of increased intracellular stress and inflammation, NFκB gains its active conformation following a signaling step involving phosphorylation of IκB, which, in turn, releases p65 (encoded by the RelA gene) leading to translocation of NFκB to the nuclear compartment for induction of specific genes involved in stress/inflammation-mediated cellular dysregulation and demise [18, 20, 27]. (cellphysiolbiochem.com)
  • In addition, curcumin activated 5' AMP‑activated protein kinase (AMPK) and suppressed p65 NF‑κB phosphorylation, as shown by western blot analysis. (spandidos-publications.com)
  • Notably, ERK5 inhibition, MEK5 deletion or NF-kB inhibition sensitized EC cells to standard EC chemotherapy (paclitaxel/carboplatin) toxicity, whereas ERK5 inhibition synergized with paclitaxel to reduce tumor xenograft growth in mice. (yyu.edu.tr)
  • Inhibition of NF-kappa B stabilizes gadd45 alpha mRNA. (cdc.gov)
  • Compound C, a potent AMPK inhibitor, abolished curcumin‑induced inhibition of NF‑κB, uPA and MMP9, suggesting that AMPK activation is responsible for curcumin‑mediated NF‑κB, uPA and MMP9 inhibition. (spandidos-publications.com)
  • Overall, the present data suggest that curcumin inhibits colon cancer cell invasion via AMPK activation and subsequent inhibition of p65 NF‑κB, uPA and MMP9. (spandidos-publications.com)
  • In contrast, in macrophages neither MyD88, Mal/TIRAP, nor I kappa B kinase 2 (IKK2) are required for NF-kappa B activation or tumor necrosis factor alpha (TNF alpha), IL-6, or IL-8 production, although Mal/TIRAP is still involved in the production of interferon beta (IFN beta). (ox.ac.uk)
  • A component of NF-kappa B transcription factor. (umassmed.edu)
  • 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. (umassmed.edu)
  • Metelev V, Zhang S, Tabatadze D, Bogdanov A. Hairpin-like fluorescent probe for imaging of NF-?B transcription factor activity. (umassmed.edu)
  • NF-κB is a transcription factor that is activated by various intra- and extra-cellular stimuli such as cytokines, oxidant-free radicals, ultraviolet irradiation, and bacterial or viral products. (abbkine.com)
  • Along these lines existing evidence supports key roles for NFκB, a transcription factor, in the regulation of cellular function under conditions of stress, inflammation and pathology of various diseases [17-23]. (cellphysiolbiochem.com)
  • The increase in the level of reactive oxygen species due to stress affects the NF-kB transcription factor in the cell. (hilarispublisher.com)
  • The transcription factor nuclear factor-κB (NF‑κB) is key in cellular processes, and the expression/activation of urokinase‑type plasminogen activator (uPA) and matrix metalloproteinase‑9 (MMP9) are crucial for cell invasion. (spandidos-publications.com)
  • NF-κB is a ubiquitous eukaryotic transcription factor, which is identified in the cytoplasm as an inactive heterotrimer consisting of p50, p65 and IκBα subunits. (spandidos-publications.com)
  • De plus, la taurine exerce son effet antiinflammatoire par l'intermediaire de la regulation de la transcription du NF-[kappa]B et de la production subsequente de mediateurs proinflammatoires par l'intermediaire de la voie de signalisation de la MAPK. (gale.com)
  • How lipopolysaccharide (LPS) signals through toll-like receptors (TLRs) to induce nuclear factor (NF)-kappa B inflammatory cytokines in sepsis remains unclear. (ox.ac.uk)
  • 05). CONCLUSION: A brief daily yogic meditation intervention may reverse the pattern of increased NF-κB-related transcription of pro-inflammatory cytokines and decreased IRF1-related transcription of innate antiviral response genes previously observed in healthy individuals confronting a significant life stressor. (virginia.edu)
  • Here, we report that a DNA-binding activity primarily consisting of the classical NF-kappa B heterodimer, p50/RelA, is induced in phagocytosing neutrophils. (univr.it)
  • El complejo FN-kappa B es un heterodímero compuesto por dos subunidades que se unen al ADN: FN-kappa B1 y relA. (bvsalud.org)
  • The NF-kappa B complex is a heterodimer composed of two DNA -binding subunits: NF-kappa B1 and relA. (bvsalud.org)
  • 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)
  • This Rat Nuclear factor-kappa B (NF-kB) ELISA Kit employs a two-site sandwich ELISA to quantitate NFKB1 in samples. (abbkine.com)
  • Rat Nuclear factor-kappa B (NF-kB) ELISA Kit has high sensitivity and excellent specificity for detection of Rat NFKB1. (abbkine.com)
  • Role of Nuclear factor kappa B (NF-κB) Signalling in Neurodegenerative Diseases: An Mechanistic Approach. (nf-kappab.com)
  • The inflammatory response mediated by nuclear factor kappa B (NF-kappa B) signaling is essential for host defense against pathogens. (sookmyung.ac.kr)
  • IKKβ-deficient mice are defective in activation of IKK and NF-κB in response to either tumor necrosis factor α or interleukin 1, and IKKα is unresponsive to IKK activators. (semanticscholar.org)
  • Numerous studies have suggested that nuclear factor-κB (NF-κB) is key in regulating a number of cellular processes, including inflammation, cellular proliferation, transformation and tumorigenesis ( 12 , 13 ). (spandidos-publications.com)
  • The effects of asbestos (1332214) on pulmonary nuclear-factor-kappa- B (NF-kB) activity were studied in rats. (cdc.gov)
  • Sulforaphane also inactivates nuclear factor kappa-B (NF-κB), a key inducer of inflammation, while activating Nrf2, which lowers inflammation in mice. (mara-labs.com)
  • IMSEAR at SEARO: Nuclear factor kappa-B and histopathology of chronic gastritis. (who.int)
  • Background: Studies suggest that nuclear factor kappa-B (NFκB) activation may be a critical event in the production of proinflammatory molecules in Helicobacter pylori-associated gastritis. (who.int)
  • Before and after treatment, serum nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß) and serum electrolytes were assessed. (bvsalud.org)
  • The TNFRSF11A gene provides instructions for making a protein called receptor activator of NF-κB (RANK). (medlineplus.gov)
  • Asbestos causes translocation of p65 protein and increases NF-kB DNA binding activity in rat lung epithelial and pleural mesothelial cells. (cdc.gov)
  • The investigation of the effect of PLGA-Curcumin Nano-formulation (Nano Curc) on the level of NF-kB subunits in cancer cells were investigated in this study. (hilarispublisher.com)
  • Ubiquitination of ECSIT is crucial for the activation of p65/p50 NF-?Bs in Toll-like receptor 4 signaling. (umassmed.edu)
  • We studied TLR5 expression in 143 unselected consecutive OPSCC tumors, and its relation to HPV-DNA and p16 status, clinicopathological parameters, and patient outcome, and studied TLR5 stimulation and consecutive NF-κB cascade activation in vitro in two human OPSCC cell lines and immortalized human keratinocytes (HaCat). (helsinki.fi)
  • In vitro, we detected NF-κΒ cascade activation in the HPV-positive OPSCC cell line and in HaCat cells, but not in the HPV-negative OPSCC cell line. (helsinki.fi)
  • A treatment with 5%(v/v) coffee extract and more than 2.5 μM pyrocatechol inhibited the LPS-induced activation of NF-κB and also significantly activated Nrf2, which acts as a negative regulator in LPS-induced inflammation. (nature.com)
  • Under these conditions, NF-kappa B activation was found to be a rapid and transient response, reaching a maximum by 10-15 min, and returning to near-basal levels by 30 min. (univr.it)
  • In neutrophils undergoing the phagocytosis of opsonized yeasts, the onset of NF-kappa B activation was paralleled by a decline in immunoreactive I kappa B-alpha protein levels, and the cellular I kappa B-alpha pool was replenished by 30 min, in agreement with our gel shift data. (univr.it)
  • We conclude that NF-kappa B activation could constitute one of the mechanisms whereby the expression of kappa B-responsive genes is enhanced in phagocytosing neutrophils. (univr.it)
  • Here we identify a new signaling axis of PKC alpha-LSD1NF-kappa B, which is critical for activation and amplification of the inflammatory response. (sookmyung.ac.kr)
  • It is concluded that while IKKγ is a stoichiometric component of the IKK complex, obligatory for NF-κB signaling, IKAP is not associated with IKKs and plays no specific role in cytokine-induced NF-σκB activation. (semanticscholar.org)
  • The results demonstrate that the functional roles of seemingly analogous domains in IKKα and IKKβ need not be equivalent and can also exhibit different contextual dependencies, and illustrates potential modes of NF-κB activation, which are not subject to the same in vivo regulatory constraints as either IKK α or IKK β. (semanticscholar.org)
  • On Day 30, ATN regressed and renal function was restored, but the cortical deposition of collagen-1 and fibronectin persisted, in association with the presence of AngII+ cells and NF-kB activation. (usp.br)
  • These changes were again associated with the presence of AngII + cells, indicative of local activation of the renin-angiotensin system, and with the activation of the NF-kB system. (usp.br)
  • The present study investigated the hypothesis that curcumin inhibits colon cancer cell invasion by modulating NF‑κB‑mediated expression and activation of uPA and MMP9. (spandidos-publications.com)
  • Although the regulatory mechanism of NF-kB signaling has been well studied, the molecular basis for epigenetic regulation of the inflammatory response is poorly understood. (sookmyung.ac.kr)
  • Together, we demonstrate that the PKC alpha-LSD1-NF-kappa B signaling cascade is crucial for epigenetic control of the inflammatory response, and targeting this signaling could be a powerful therapeutic strategy for systemic inflammatory diseases, including sepsis. (sookmyung.ac.kr)
  • The role of NFκB appears to be only in the initial stages of gastritis, there is no role for the molecule in the development of chronic inflammation or atrophy. (who.int)
  • No presente estudo, investigamos o comportamento das vias NLRP3 e NF-kB na progressão para DRC da LRA induzida por GT. (usp.br)
  • NF-kappaB binding was assessed using the electromobility shift assay, and activity was measured using a luciferase reporter vector. (nih.gov)
  • The effects on nuclear protein binding to NF- kB DNA consensus sequences were examined using an electrophoretic mobility shift assay. (cdc.gov)
  • Independentemente do insulto que desencadeou a LRA, a intensa necrose tubular promove a ativação de vias da imunidade inata, como a TLR4/NF-kB e a do inflamassomaNLRP3/IL-1beta. (usp.br)
  • No Dia 1, os ratos GT exibiram albuminúria acentuada e retenção de creatinina, alterações na fração de excreção de Na+ e K+, necrose tubular aguda (NTA) com aumento da abundância renal de KIM-1, lesões glomerulares, inflamação intersticial e ativação das vias TLR4/NF-kB eNLRP3/IL-1beta. (usp.br)
  • over 200 known genes are targets of NF-κB in various cell types, under specific conditions. (abbkine.com)
  • Structure of an IkappaBalpha/NF-kappaB complex. (embl.de)
  • Published evidence also implicates NFκB in regulation of islet beta cell function in health and diabetes [19, 24-26]. (cellphysiolbiochem.com)
  • Hyldahl RD, Schwartz LM, Clarkson PM. NF-KB activity functions in primary pericytes in a cell- and non-cell-autonomous manner to affect myotube formation. (umassmed.edu)
  • Elevated NF-κΒ activity is detectable in several cancers and regulates cancer development and progression. (helsinki.fi)
  • Flagellin served to stimulate TLR5 in cultured cells, followed by analysis of the activity of the NF-κB signaling cascade with In-Cell Western for IκΒ and p-IκΒ. (helsinki.fi)
  • Our results suggest that elevated TLR5 immunoexpression may be related to reduced NF-κΒ activity in HPV-negative OPSCC. (helsinki.fi)
  • The binding activity of NF‑κB to DNA was examined and western blotting and quantitative polymerase reaction was performed to detect the effect of curcumin on the expression of uPA and MMP9. (spandidos-publications.com)
  • The present results revealed that curcumin significantly decreased the expression of uPA and MMP9 and NF‑κB DNA binding activity. (spandidos-publications.com)
  • Materials and Methods: This study examines the expression and activity of NFκB in situ in antral biopsies of 42 consecutive patients with immunohistochemical techniques. (who.int)
  • Results: NFκB was highly expressed in the gastric epithelial cells. (who.int)
  • It shows a stack of six IkappaBalpha ankyrin repeats facing the C-terminal domains of the NF-kappaB Rel homology regions. (rcsb.org)
  • The position of the sixth ankyrin repeat shows that full-length IkappaBalpha will occlude the NF-kappaB DNA-binding cleft. (rcsb.org)
  • We propose the ERK5/NF-kappa B axis as new target for EC treatment. (yyu.edu.tr)
  • The effect of Nano-Curc on the ratios of four sub-units of NF-kB including P65, P52, P50 and C-Rel were evaluated on MCF-7 breast cancer cell lines which were pre-treated with paclitaxel. (hilarispublisher.com)
  • A better understanding of the NF-kB structure and mechanism of action will play an important role in the reduction of cellular stress and hence the emergence of new approaches and mechanisms of action in eliminating the negative effects of stress. (hilarispublisher.com)
  • Zhang S, Metelev V, Tabatadze D, Zamecnik P, Bogdanov A. Near-infrared fluorescent oligodeoxyribonucleotide reporters for sensing NF-kappaB DNA interactions in vitro. (umassmed.edu)
  • In-vitro treatment with crocidolite caused significant dose related increases in p65 binding to NF-kB consensus DNA sequences in both RLE and RPM cells. (cdc.gov)
  • It is seen in approximately 50% of patients with mutations in the neurofibromatosis type 2 (NF-2) gene. (abta.org)
  • A Tax mutant that did not activate NF-{kappa}B failed to activate cyclin D1 and D2 promoters. (mdc-berlin.de)