A signal-transducing adaptor protein that associates with TNF RECEPTOR complexes. It contains a death effector domain that can interact with death effector domains found on INITIATOR CASPASES such as CASPASE 8 and CASPASE 10. Activation of CASPASES via interaction with this protein plays a role in the signaling cascade that leads to APOPTOSIS.
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 family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.
A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
A large group of proteins that control APOPTOSIS. This family of proteins includes many ONCOGENE PROTEINS as well as a wide variety of classes of INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS such as CASPASES.
A long pro-domain caspase that contains a death effector domain in its pro-domain region. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS. Caspase 10 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
A long pro-domain caspase that contains a death effector domain in its pro-domain region. Caspase 8 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS.
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.
An APOPTOSIS-regulating protein that is structurally related to CASPASE 8 and competes with CASPASE 8 for binding to FAS ASSOCIATED DEATH DOMAIN PROTEIN. Two forms of CASP8 and FADD-like apoptosis regulating protein exist, a long form containing a caspase-like enzymatically inactive domain and a short form which lacks the caspase-like domain.
A conserved class of proteins that control APOPTOSIS in both VERTEBRATES and INVERTEBRATES. IAP proteins interact with and inhibit CASPASES, and they function as ANTI-APOPTOTIC PROTEINS. The protein class is defined by an approximately 80-amino acid motif called the baculoviral inhibitor of apoptosis repeat.
A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 9 is activated during cell stress by mitochondria-derived proapoptotic factors and by CARD SIGNALING ADAPTOR PROTEINS such as APOPTOTIC PROTEASE-ACTIVATING FACTOR 1. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.
Splitting the DNA into shorter pieces by endonucleolytic DNA CLEAVAGE at multiple sites. It includes the internucleosomal DNA fragmentation, which along with chromatin condensation, are considered to be the hallmarks of APOPTOSIS.
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 member of the Bcl-2 protein family and homologous partner of C-BCL-2 PROTO-ONCOGENE PROTEIN. It regulates the release of CYTOCHROME C and APOPTOSIS INDUCING FACTOR from the MITOCHONDRIA. Several isoforms of BCL2-associated X protein occur due to ALTERNATIVE SPLICING of the mRNA for this protein.
An in situ method for detecting areas of DNA which are nicked during APOPTOSIS. Terminal deoxynucleotidyl transferase is used to add labeled dUTP, in a template-independent manner, to the 3 prime OH ends of either single- or double-stranded DNA. The terminal deoxynucleotidyl transferase nick end labeling, or TUNEL, assay labels apoptosis on a single-cell level, making it more sensitive than agarose gel electrophoresis for analysis of DNA FRAGMENTATION.
A cell line derived from cultured tumor cells.
Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.
A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.
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.
An inhibitor of apoptosis protein that is translated by a rare cap-independent mechanism. It blocks caspase-mediated cellular destruction by inhibiting CASPASE 3; CASPASE 7; and CASPASE 9.
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.
A flavoprotein that functions as a powerful antioxidant in the MITOCHONDRIA and promotes APOPTOSIS when released from the mitochondria. In mammalian cells AIF is released in response to pro-apoptotic protein members of the bcl-2 protein family. It translocates to the CELL NUCLEUS and binds DNA to stimulate CASPASE-independent CHROMATIN condensation.
Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th 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.
A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 7; CASPASE 8; and CASPASE 10. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
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.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
Established cell cultures that have the potential to propagate indefinitely.
Cytochromes of the c type that are found in eukaryotic MITOCHONDRIA. They serve as redox intermediates that accept electrons from MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III and transfer them to MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV.
Transport proteins that carry specific substances in the blood or across cell membranes.
A member of the bcl-2 protein family that plays a role in the regulation of APOPTOSIS. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING of the BCL2L1 mRNA and are referred to as Bcl-XS and Bcl-XL.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.
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.
A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Activation of this enzyme can occur via the interaction of its caspase recruitment domain with CARD SIGNALING ADAPTOR PROTEINS. Caspase 2 plays a role in APOPTOSIS by cleaving and activating effector pro-caspases. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
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.
Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.
A transmembrane-protein belonging to the TNF family of intercellular signaling proteins. It is a widely expressed ligand that activates APOPTOSIS by binding to TNF-RELATED APOPTOSIS-INDUCING LIGAND RECEPTORS. The membrane-bound form of the protein can be cleaved by specific CYSTEINE ENDOPEPTIDASES to form a soluble ligand form.
A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
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.
Tumor necrosis factor receptor family members that are widely expressed and play a role in regulation of peripheral immune responses and APOPTOSIS. The receptors are specific for TNF-RELATED APOPTOSIS-INDUCING LIGAND and signal via conserved death domains that associate with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
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.
Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.
Intracellular signaling adaptor proteins that bind to the cytoplasmic death domain region found on DEATH DOMAIN RECEPTORS. Many of the proteins in this class take part in intracellular signaling from TUMOR NECROSIS FACTOR RECEPTORS.
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.
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.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. It plays a role in INFLAMMATION by catalytically converting the inactive forms of CYTOKINES such as interleukin-1beta to their active, secreted form. Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Glycoproteins found on the membrane or surface of cells.
A family of cell surface receptors that signal via a conserved domain that extends into the cell CYTOPLASM. The conserved domain is referred to as a death domain due to the fact that many of these receptors are involved in signaling APOPTOSIS. Several DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS can bind to the death domains of the activated receptors and through a complex series of interactions activate apoptotic mediators such as CASPASES.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.
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 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 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 group of cytochromes with covalent thioether linkages between either or both of the vinyl side chains of protoheme and the protein. (Enzyme Nomenclature, 1992, p539)
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
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.
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 relationship between the dose of an administered drug and the response of the organism to the drug.
Elements of limited time intervals, contributing to particular results or situations.
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.
A family of serine-threonine kinases that plays a role in intracellular signal transduction by interacting with a variety of signaling adaptor proteins such as CRADD SIGNALING ADAPTOR PROTEIN; TNF RECEPTOR-ASSOCIATED FACTOR 2; and TNF RECEPTOR-ASSOCIATED DEATH DOMAIN PROTEIN. Although they were initially described as death domain-binding adaptor proteins, members of this family may contain other protein-binding domains such as those involving caspase activation and recruitment.
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.
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.
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.
A multi-domain mitochondrial membrane protein and member of the bcl-2 Protein family. Bak protein interacts with TUMOR SUPPRESSOR PROTEIN P53 and promotes APOPTOSIS.
A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.
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 promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)
A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 3 and CASPASE 10. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
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.
The voltage difference, normally maintained at approximately -180mV, across the INNER MITOCHONDRIAL MEMBRANE, by a net movement of positive charge across the membrane. It is a major component of the PROTON MOTIVE FORCE in MITOCHONDRIA used to drive the synthesis of ATP.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
The B-cell leukemia/lymphoma-2 genes, responsible for blocking apoptosis in normal cells, and associated with follicular lymphoma when overexpressed. Overexpression results from the t(14;18) translocation. The human c-bcl-2 gene is located at 18q24 on the long arm of chromosome 18.
Enzymes that catalyze the formation of acyl-CoA derivatives. EC 6.2.1.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
A CARD signaling adaptor protein that plays a role in the mitochondria-stimulated apoptosis (APOPTOSIS, INTRINSIC PATHWAY). It binds to CYTOCHROME C in the CYTOSOL to form an APOPTOSOMAL PROTEIN COMPLEX and activates INITIATOR CASPASES such as CASPASE 9.
A 34 kDa signal transducing adaptor protein that associates with TUMOR NECROSIS FACTOR RECEPTOR TYPE 1. It facilitates the recruitment of signaling proteins such as TNF RECEPTOR-ASSOCIATED FACTOR 2 and FAS ASSOCIATED DEATH DOMAIN PROTEIN to the receptor complex.
A family of enzymes that catalyze the stereoselective, regioselective, or chemoselective syn-dehydrogenation reactions. They function by a mechanism that is linked directly to reduction of molecular OXYGEN.
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.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
A member of the myeloid leukemia factor (MLF) protein family with multiple alternatively spliced transcript variants encoding different protein isoforms. In hematopoietic cells, it is located mainly in the nucleus, and in non-hematopoietic cells, primarily in the cytoplasm with a punctate nuclear localization. MLF1 plays a role in cell cycle differentiation.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Members of the class of neutral glycosphingolipids. They are the basic units of SPHINGOLIPIDS. They are sphingoids attached via their amino groups to a long chain fatty acyl group. They abnormally accumulate in FABRY DISEASE.
Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.
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.
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)
A tumor necrosis factor receptor subtype that has specificity for TUMOR NECROSIS FACTOR ALPHA and LYMPHOTOXIN ALPHA. It is constitutively expressed in most tissues and is a key mediator of tumor necrosis factor signaling in the vast majority of cells. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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).
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.
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.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
A pro-apoptotic protein and member of the Bcl-2 protein family that is regulated by PHOSPHORYLATION. Unphosphorylated Bad protein inhibits the activity of BCL-XL PROTEIN.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
A subtype of caspases that contain long pro-domain regions that regulate the activation of the enzyme. The pro-domain regions contain protein-protein interaction motifs that can interact with specific signaling adaptor proteins such as DEATH DOMAIN RECEPTORS; DED SIGNALING ADAPTOR PROTEINS; and CARD SIGNALING ADAPTOR PROTEINS. Once activated, the initiator caspases can activate other caspases such as the EFFECTOR CASPASES.
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.
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 disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
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)
The action of a drug in promoting or enhancing the effectiveness of another drug.
A human cell line established from a diffuse histiocytic lymphoma (HISTIOCYTIC LYMPHOMA, DIFFUSE) and displaying many monocytic characteristics. It serves as an in vitro model for MONOCYTE and MACROPHAGE differentiation.
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
A signal transducing tumor necrosis factor receptor associated factor that is involved in TNF RECEPTOR feedback regulation. It is similar in structure and appears to work in conjunction with TNF RECEPTOR-ASSOCIATED FACTOR 2 to inhibit APOPTOSIS.
A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories for solving biological problems including manipulation of models and datasets.
Proteins prepared by recombinant DNA technology.
A process that includes the determination of AMINO ACID SEQUENCE of a protein (or peptide, oligopeptide or peptide fragment) and the information analysis of the sequence.
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.
Enzymes that catalyze the joining of two molecules by the formation of a carbon-sulfur bond. EC 6.2.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
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.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
A family of serine proteinase inhibitors which are similar in amino acid sequence and mechanism of inhibition, but differ in their specificity toward proteolytic enzymes. This family includes alpha 1-antitrypsin, angiotensinogen, ovalbumin, antiplasmin, alpha 1-antichymotrypsin, thyroxine-binding protein, complement 1 inactivators, antithrombin III, heparin cofactor II, plasminogen inactivators, gene Y protein, placental plasminogen activator inhibitor, and barley Z protein. Some members of the serpin family may be substrates rather than inhibitors of SERINE ENDOPEPTIDASES, and some serpins occur in plants where their function is not known.
Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.
Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
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.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
A family of proteins that were originally identified by their ability to cause NECROSIS of NEOPLASMS. Their necrotic effect on cells is mediated through TUMOR NECROSIS FACTOR RECEPTORS which induce APOPTOSIS.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of LYSOSOMES containing cellular components in the process of digestion; it plays an important role in BIOLOGICAL METAMORPHOSIS of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states.
A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.
Tumors or cancer of the human BREAST.
A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.
A subclass of caspases that contain short pro-domain regions. They are activated by the proteolytic action of INITIATOR CASPASES. Once activated they cleave a variety of substrates that cause APOPTOSIS.
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.
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.
In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
A 150-kDa MAP kinase kinase kinase that may play a role in the induction of APOPTOSIS. It has specificity for MAP KINASE KINASE 3; MAP KINASE KINASE 4; and MAP KINASE KINASE 6.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins.
The segment of LARGE INTESTINE between the CECUM and the TRANSVERSE COLON. It passes cephalad from the cecum to the caudal surface of the right lobe of the LIVER where it bends sharply to the left, forming the right colic flexure.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
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.
Interruption or suppression of the expression of a gene at transcriptional or translational levels.
Sequential operating programs and data which instruct the functioning of a digital computer.
Intracellular signaling peptides and proteins that bind directly or indirectly to the cytoplasmic portion of TUMOR NECROSIS FACTOR RECEPTORS.
A family of non-enveloped viruses infecting mammals (MASTADENOVIRUS) and birds (AVIADENOVIRUS) or both (ATADENOVIRUS). Infections may be asymptomatic or result in a variety of diseases.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
CULTURE MEDIA free of serum proteins but including the minimal essential substances required for cell growth. This type of medium avoids the presence of extraneous substances that may affect cell proliferation or unwanted activation of cells.
Quaternary ammonium analog of ethidium; an intercalating dye with a specific affinity to certain forms of DNA and, used as diiodide, to separate them in density gradients; also forms fluorescent complexes with cholinesterase which it inhibits.
Short fragments of DNA or RNA that are used to alter the function of target RNAs or DNAs to which they hybridize.
Peptides composed of between two and twelve amino acids.
Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.
High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.
A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.
The process by which chemical compounds provide protection to cells against harmful agents.
The two lipoprotein layers in the MITOCHONDRION. The outer membrane encloses the entire mitochondrion and contains channels with TRANSPORT PROTEINS to move molecules and ions in and out of the organelle. The inner membrane folds into cristae and contains many ENZYMES important to cell METABOLISM and energy production (MITOCHONDRIAL ATP SYNTHASE).
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.
Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to a serine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and serine and 2 moles of fatty acids.
Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.
The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.
A CCAAT-enhancer binding protein that is induced by DNA DAMAGE and growth arrest. It serves as a dominant negative inhibitor of other CCAAT-enhancer binding proteins.
Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.
Tumors or cancer of the COLON.
Tumors or cancer of the PROSTATE.
A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)
The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
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).
Penetrating, high-energy electromagnetic radiation emitted from atomic nuclei during NUCLEAR DECAY. The range of wavelengths of emitted radiation is between 0.1 - 100 pm which overlaps the shorter, more energetic hard X-RAYS wavelengths. The distinction between gamma rays and X-rays is based on their radiation source.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Cellular DNA-binding proteins encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis.
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.
The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.
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.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
Tumors or cancer of the LUNG.
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.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
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.

Fas/Apo [apoptosis]-1 and associated proteins in the differentiating cerebral cortex: induction of caspase-dependent cell death and activation of NF-kappaB. (1/700)

The developing cerebral cortex undergoes a period of substantial cell death. The present studies examine the role of the suicide receptor Fas/Apo[apoptosis]-1 in cerebral cortical development. Fas mRNA and protein are transiently expressed in subsets of cells within the developing rat cerebral cortex during the peak period of apoptosis. Fas-immunoreactive cells were localized in close proximity to Fas ligand (FasL)-expressing cells. The Fas-associated signaling protein receptor interacting protein (RIP) was expressed by some Fas-expressing cells, whereas Fas-associated death domain (FADD) was undetectable in the early postnatal cerebral cortex. FLICE-inhibitory protein (FLIP), an inhibitor of Fas activation, was also expressed in the postnatal cerebral cortex. Fas expression was more ubiquitous in embryonic cortical neuroblasts in dissociated culture compared to in situ within the developing brain, suggesting that the environmental milieu partly suppresses Fas expression at this developmental stage. Furthermore, FADD, RIP, and FLIP were also expressed by subsets of dissociated cortical neuroblasts in culture. Fas activation by ligand (FasL) or anti-Fas antibody induced caspase-dependent cell death in primary embryonic cortical neuroblast cultures. The activation of Fas was also accompanied by a rapid downregulation of Fas receptor expression, non-cell cycle-related incorporation of nucleic acids and nuclear translocation of the RelA/p65 subunit of the transcription factor NF-kappaB. Together, these data suggest that adult cortical cell number may be established, in part, by an active process of receptor-mediated cell suicide, initiated in situ by killer (FasL-expressing) cells and that Fas may have functions in addition to suicide in the developing brain.  (+info)

Equine herpesvirus-2 E10 gene product, but not its cellular homologue, activates NF-kappaB transcription factor and c-Jun N-terminal kinase. (2/700)

We have previously reported on the death effector domain containing E8 gene product from equine herpesvirus-2, designated FLICE inhibitory protein (v-FLIP), and on its cellular homologue, c-FLIP, which inhibit the activation of caspase-8 by death receptors. Here we report on the structure and function of the E10 gene product of equine herpesvirus-2, designated v-CARMEN, and on its cellular homologue, c-CARMEN, which contain a caspase-recruiting domain (CARD) motif. c-CARMEN is highly homologous to the viral protein in its N-terminal CARD motif but differs in its C-terminal extension. v-CARMEN and c-CARMEN interact directly in a CARD-dependent manner yet reveal different binding specificities toward members of the tumor necrosis factor receptor-associated factor (TRAF) family. v-CARMEN binds to TRAF6 and weakly to TRAF3 and, upon overexpression, potently induces the c-Jun N-terminal kinase (JNK), p38, and nuclear factor (NF)-kappaB transcriptional pathways. c-CARMEN or truncated versions thereof do not appear to induce JNK and NF-kappaB activation by themselves, nor do they affect the JNK and NF-kappaB activating potential of v-CARMEN. Thus, in contrast to the cellular homologue, v-CARMEN may have additional properties in its unique C terminus that allow for an autonomous activator effect on NF-kappaB and JNK. Through activation of NF-kappaB, v-CARMEN may regulate the expression of the cellular and viral genes important for viral replication.  (+info)

Cell death attenuation by 'Usurpin', a mammalian DED-caspase homologue that precludes caspase-8 recruitment and activation by the CD-95 (Fas, APO-1) receptor complex. (3/700)

Apoptotic cell suicide initiated by ligation of CD95 (Fas/APO-1) occurs through recruitment, oligomerization and autocatalytic activation of the cysteine protease, caspase-8 (MACH, FLICE, Mch5). An endogenous mammalian regulator of this process, named Usurpin, has been identified (aliases for Usurpin include CASH, Casper, CLARP, FLAME-1, FLIP, I-FLICE and MRIT). This protein is ubiquitously expressed and exists as at least three isoforms arising by alternative mRNA splicing. The Usurpin gene is comprised of 13 exons and is clustered within approximately 200 Kb with the caspase-8 and -10 genes on human chromosome 2q33-34. The Usurpin polypeptide has features in common with pro-caspase-8 and -10, including tandem 'death effector domains' on the N-terminus of a large subunit/small subunit caspase-like domain, but it lacks key residues that are necessary for caspase proteolytic activity, including the His and Cys which form the catalytic substrates diad, and residues that stabilize the P1 aspartic acid in substrates. Retro-mutation of these residues to functional caspase counterparts failed to restore proteolytic activity, indicating that other determinants also ensure the absence of catalytic potential. Usurpin heterodimerized with pro-caspase-8 in vitro and precluded pro-caspase-8 recruitment by the FADD/MORT1 adapter protein. Cell death induced by CD95 (Fas/APO-1) ligation was attenuated in cells transfected with Usurpin. In vivo, a Usurpin deficit was found in cardiac infarcts where TUNEL-positive myocytes and active caspase-3 expression were prominent following ischemia/reperfusion injury. In contrast, abundant Usurpin expression (and a caspase-3 deficit) occurred in surrounding unaffected cardiac tissue, suggesting reciprocal regulation of these pro- and anti-apoptotic molecules in vivo. Usurpin thus appears to be an endogenous modulator of apoptosis sensitivity in mammalian cells, including the susceptibility of cardiac myocytes to apoptotic death following ischemia/ reperfusion injury.  (+info)

TCR engagement regulates differential responsiveness of human memory T cells to Fas (CD95)-mediated apoptosis. (4/700)

In this work, we have tried to establish whether human memory T cells may be protected from Fas (CD95)-induced apoptosis when correctly activated by Ag, and not protected when nonspecifically or incorrectly activated. In particular, we wanted to investigate the molecular mechanisms that regulate the fate of memory T cells following an antigenic challenge. To address this issue, we chose an experimental system that closely mimics physiological T cell activation such as human T cell lines and clones specific for viral peptides or alloantigens. We demonstrate that memory T cells acquire an activation-induced cell death (AICD)-resistant phenotype when TCRs are properly engaged by specific Ag bound to MHC molecules. Ag concentration and costimulation are critical parameters in regulating the protective effect. The analysis of the mechanisms involved in the block of CD95 signal transduction pathways revealed that the crucial events are the inhibition of CD95-associated IL-1beta-converting enzyme (ICE)-like protease (FLICE) activation and poly(ADP)-ribose polymerase cleavage, and the mRNA expression of FLICE-like inhibitory protein. Furthermore, we have observed that TCR-mediated neosynthesis of FLICE-like inhibitory protein mRNA is suppressed either by protein tyrosine kinase inhibitors or cyclosporin A. In conclusion, the present analysis of the effects of TCR triggering on the regulation of AICD suggests that AICD could be inhibited in human memory T cells activated in vivo by a foreign Ag, but may become operative when the Ag has been cleared.  (+info)

Transcriptional analysis of human herpesvirus-8 open reading frames 71, 72, 73, K14, and 74 in a primary effusion lymphoma cell line. (5/700)

We examined the transcription and splicing of open reading frames (ORFs) 71 (K13)-74 of human herpesvirus-8 (HHV-8) in the primary effusion lymphoma cell line BCP-1 (latently infected with HHV-8), using a combination of NORTHERN blot analysis, RT-PCR, and rapid amplification of cDNA ends (PCR-RACE). The three genes encoded by ORFs 71, 72, and 73 [viral FLICE inhibitory protein (v-FLIP), v-cyclin, latent nuclear antigen (LNA)] are transcribed from a common transcription start site in BCP-1 cells uninduced (latent) or induced (lytic) with n-butyrate. The resulting transcript is spliced to yield a 5.32-kb message encoding LNA, v-cyclin, and v-FLIP and a 1.7-kb bicistronic message encoding v-cyclin and v-FLIP. The two genes encoded by ORFs K14 and 74 (v-Ox2 and v-GPCR) are transcribed as a 2.7-kb bicistronic transcript that is induced with n-butyrate. A small (149-bp) intron is spliced from the intragenic noncoding region immediately before the v-GPCR initiating codon. Examination of sequence elements in the promoter of the LNA/v-cyclin/v-FLIP operon revealed TAATGARAT and Octamer binding motifs characteristic of herpesvirus immediate-early genes. Sequence elements in the v-Ox2/v-GPCR promoter included AP1 and Zta-like (EBV Zebra transactivator) binding motifs consistent with the n-butyrate induction of this operon.  (+info)

Cell cycle-dependent regulation of FLIP levels and susceptibility to Fas-mediated apoptosis. (6/700)

Activation-induced cell death of peripheral T cells results from the interaction between Fas and Fas ligand. Resting peripheral T cells are resistant to Fas-induced apoptosis and become susceptible only after their activation. We have investigated the molecular mechanism mediating the sensitization of resting peripheral T cells to Fas-mediated apoptosis following TCR stimulation. TCR activation decreases the steady state protein levels of FLIP (FLICE-like inhibitory protein), an inhibitor of the Fas signaling pathway. Reconstitution of intracellular FLIP levels by the addition of a soluble HIV transactivator protein-FLIP chimera completely restores resistance to Fas-mediated apoptosis in TCR primary T cells. Inhibition of IL-2 production by cyclosporin A, or inhibition of IL-2 signaling by rapamycin or anti-IL-2 neutralizing Abs prevents the decrease in FLIP levels and confers resistance to Fas-mediated apoptosis following T cell activation. Using cell cycle-blocking agents, we demonstrate that activated T cells arrested in G1 phase contain high levels of FLIP protein, whereas activated T cells arrested in S phase have decreased FLIP protein levels. These findings link regulation of FLIP protein levels with cell cycle progression and provide an explanation for the increase in TCR-induced apoptosis observed during the S phase of the cell cycle.  (+info)

Relation of TNF-related apoptosis-inducing ligand (TRAIL) receptor and FLICE-inhibitory protein expression to TRAIL-induced apoptosis of melanoma. (7/700)

Past studies have shown that apoptosis mediated by TNF-related apoptosis-inducing ligand (TRAIL) is regulated by the expression of two death receptors [TRAIL receptor 1 (TRAIL-R1) and TRAIL-R2] and two decoy receptors (TRAIL-R3 and TRAIL-R4) that inhibit apoptosis. In previous studies, we have shown that TRAIL but not other members of the tumor necrosis factor family induce apoptosis in approximately two-thirds of melanoma cell lines. Here, we examined whether the expression of TRAIL-R at the mRNA and protein level in a panel of 28 melanoma cell lines and melanocytes correlated with their sensitivity to TRAIL-induced apoptosis. We report that at least three factors appear to underlie the variability in TRAIL-induced apoptosis. (a) Four of nine cell lines that were insensitive to TRAIL-induced apoptosis failed to express death receptors, and in two instances, lines were devoid of all TRAIL-Rs. Southern analysis suggested this was due to loss of the genes for the death receptors. (b) Despite the presence of mRNA for the TRAIL-R, some of the lines failed to express TRAIL-R protein on their surface. This was evident for TRAIL-R1 and more so for the TRAIL decoy receptors TRAIL-R3 and -R4. Studies on permeabilized cells revealed that the receptors were located within the cytoplasm and redistribution from the cytoplasm may represent a posttranslational control mechanism. (c) Surface expression of TRAIL-R1 and -R2 (but not TRAIL-R3 and -R4) showed an overall correlation with TRAIL-induced apoptosis. However, certain melanoma cell lines and clones were relatively resistant to TRAIL-induced apoptosis despite the absence of decoy receptors and moderate levels of TRAIL-R1 and -R2 expression. This may indicate the presence of inhibitors within the cells, but resistance to apoptosis could not be correlated with expression of the caspase inhibitor FLICE-inhibitory protein. mRNA for another TRAIL receptor, osteoprotegerin, was expressed in 22 of the melanoma lines but not on melanocytes. Its role in induction of apoptosis remains to be studied. These results appear to have important implications for future clinical studies on TRAIL.  (+info)

Dynamic correlation of apoptosis and immune activation during treatment of HIV infection. (8/700)

T cells from HIV infected patients undergo spontaneous apoptosis at a faster rate than those from uninfected patients, are abnormally susceptible to activation induced cell death (AICD), and undergo increased apoptosis in response to Fas receptor ligation. These observations have led to the hypothesis CD4 T cell apoptosis may be a mechanism of CD4 T cell depletion and the pathogenesis of AIDS. Successful treatment of HIV infected patients is accompanied by quantitative and qualitative improvements in immune function reflecting at least partial reversibility of the underlying pathogenesis of HIV. In this report we correlate improvements in markers of immune function with a decrease in apoptosis, and changes in its regulation. Therapy with nelfinavir plus saquinavir in combination with two nucleoside analogue inhibitors of reverse transcriptase dramatically reduces plasma viremia and increases CD4 T cell counts. Coincident with these improvements, CD38 and HLA-DR coexpression on both CD4 and CD8 T cells decrease, and CD45RA and CD62L coexpression increase. Furthermore, spontaneous apoptosis decreases in both CD4 and CD8 T cells (CD4 apoptosis 17.4 vs 2.6%, P=0.005; CD8 apoptosis 15.0 vs 1.0%, P<0.001), as does both Fas mediated apoptosis (CD4 apoptosis 19.0 vs 3.5%, P=0.03; CD8 apoptosis 13.7 vs 1.5%, P=0.002) and CD3 induced AICD (CD4 apoptosis 13.7 vs 3.2%, P=0.001; CD8 apoptosis 29 vs 2.2%, P=0.08). Changes in apoptosis are not associated with changes in Fas receptor expression, but are significantly correlated with changes in activation marker profiles. Although this suggests a possible regulatory role for the apoptosis inhibitory protein FLIP, direct assessment did not reveal quantitative differences in FLIP expression between apoptosis resistant PBL's from HIV negative patients, and apoptosis sensitive PBL's from HIV positive patients. These findings support the hypothesis that apoptosis mediates HIV induced CD4 T cell depletion, but indicate the need for further studies into the molecular regulation of HIV induced apoptosis.  (+info)

Induction of apoptosis is the most studied cell death process and it is a tightly regulated physiological event that enables elimination of damaged and unwanted cells. Apoptosis can be induced via activation of either the intrinsic or the extrinsic signalling pathway. The intrinsic pathway involves activation of the mitochondria by stress stimuli, whereas the extrinsic pathway is triggered by ligand induced activation of death receptors such as Fas. Apoptosis induction via Fas activation plays an important role in the function of cytotoxic T lymphocytes and in the control of immune cell homeostasis.. Several studies have shown that anticancer therapies require functional cell death signalling pathways. Irradiation based therapy has been successful in treatment of several malignancies but the usage of high doses has been associated with side effects. Therefore, low dose therapies, that either is optimized for specific delivery or administrated in combination with other treatments, are promising ...
Hodgkins lymphoma is one of the most common lymphoid cancers, particularly among young adults. Although there have been dramatic improvements in the treatment of Hodgkins lymphoma, leading to high cure rates in some groups, current combination chemotherapy regimes are associated with significant secondary complications in long-term survivors. Furthermore, although a proportion of patients with Hodgkins lymphoma will be cured, there still remains a significant rate of relapse and also a smaller proportion of poor responders who will go on to die of their disease. Therefore, developments in the treatment of Hodgkins lymphoma must be directed at improving cure rates and reducing the burden of secondary complications. In recent years, the underlying pathogenesis of Hodgkins lymphoma has become better understood. In particular, it is emerging that a key pathogenic event in Hodgkins lymphoma is protection from Fas-induced cell death. Recent studies by the authors group, and others, have ...
O15519: CASP8 and FADD-like apoptosis regulator; Caspase homolog; CASH; Caspase-eight-related protein; Casper; Caspase-like apoptosis regulatory protein; CLARP; Cellular FLICE-like inhibitory protein; c-FLIP; FADD-like antiapoptotic molecule 1; FLAME-1; Inhibitor of FLICE; I-FLICE; MACH-related inducer of toxicity; MRIT; Usurpin; CASP8 and FADD-like apoptosis regulator subunit p43; CASP8 and FADD-like apoptosis regulator subunit p12; ...
758 Fas is a well characterized member of the death receptor family and its expression correlates with overall patient survival in Cholangiocarcinoma (Shimonishi et al;Hepatology 2000). Cellular FLICE-like inhibitory protein (c-FLIP) is an anti-apoptotic protein that blocks the activation of caspase 8 and apoptosis signaling through death inducing signaling complex (DISC). In our laboratory, we have established a unique Cholangiocarcinoma system with two cell populations that are sensitive (high surface Fas expression) or resistant (low surface Fas expression) to Fas-induced apoptosis (Pan et al; 1999; Am J Path). Fas sensitive, but not Fas resistant cells, undergo apoptosis when exposed to calmodulin (CaM) antagonists via a mechanism similar to Fas-induced death signaling. In an attempt to delineate the role of CaM in Fas mediated signaling, we previously demonstrated a direct interaction between CaM and Fas (Ahn et a; J Biol Chem. 2004) and that CaM is recruited to Fas-induced DISC ...
We examined whether the multikinase inhibitor sorafenib and histone deacetylase inhibitors (HDACI) interact to kill pancreatic carcinoma cells and determined the impact of inhibiting BCL-2 family function on sorafenib and HDACI lethality. The lethality of sorafenib was enhanced in pancreatic tumor cells in a synergistic fashion by pharmacologically achievable concentrations of the HDACIs vorinostat or sodium valproate. Overexpression of cellular FLICE-like inhibitory protein (c-FLIP-s) or knockdown of CD95 suppressed the lethality of the sorafenib/HDACI combination (sorafenib + HDACI). In immunohistochemical analyses or using expression of fluorescence-tagged proteins, treatment with sorafenib and vorinostat together (sorafenib + vorinostat) promoted colocalization of CD95 with caspase 8 and CD95 association with the endoplasmic reticulum markers calnexin, ATG5, and Grp78/BiP. In cells lacking CD95 expression or in cells expressing c-FLIP-s, the lethality of sorafenib + HDACI exposure was ...
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Cellular caspase-8 (FLICE)-like inhibitory protein (cFLIP) was originally identified as an inhibitor of death-receptor signalling. However, this Review discusses new data indicating that cFLIP is also required for the survival and proliferation of T cells following T-cell-receptor stimulation. Cellular caspase-8 (FLICE)-like inhibitory protein (cFLIP) was originally identified as an inhibitor of death-receptor signalling through competition with caspase-8 for recruitment to FAS-associated via death domain (FADD). More recently, it has been determined that both cFLIP and caspase-8 are required for the
Death receptor (DR) ligation can lead to divergent signaling pathways causing either caspase-mediated cell death or cell proliferation and inflammation. These variations in cellular fate are determined by adaptor proteins that are recruited to the DR signaling complex. FLICE inhibitory protein (FLIP) is an established inhibitor of caspase-8-mediated apoptosis, and it is also involved in NF-kappa B
Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) is a novel cytokine displaying selective apoptosis-inducing activity in transformed cells without harming normal cells. The present studies focused on clarifying the mechanism(s) by which glutathione S-transferase (GST)-MDA-7 altered cell survival of human renal carcinoma cells in vitro. GST-MDA-7 caused plasma membrane clustering of CD95 and the association of CD95 with procaspase-8. GST-MDA-7 lethality was suppressed by inhibition of caspase-8 or by overexpression of short-form cellular FLICE inhibitory protein, but only weakly by inhibition of cathepsin proteases. GST-MDA-7-induced CD95 clustering (and apoptosis) was blocked by knockdown of acidic sphingomyelinase or, to a greater extent, ceramide synthase-6 expression. GST-MDA-7 killing was, in parallel, dependent on inactivation of extracellular signal-regulated kinase 1/2 and on CD95-induced p38 mitogen-activated protein kinase and c-jun NH2-terminal kinase-1/2 ...
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To more characterize the expression of c-FLIP isoforms in human Th cells, we examined the kinetics of c-FLIPS and c-FLIPL on protein amount throughout the early differentiation. c-FLIPL is expressed in Thp cells while c-FLIPS expression becomes noticeable shortly right after activation (Determine 2A). However, we could not detect c-FLIPR isoform on protein degree, which […]. Continue reading ...
Rabbit polyclonal antibody raised against synthetic peptide of CFLAR. A synthetic peptide corresponding to C-terminus of human CFLAR. (PAB8648) - Products - Abnova
In addition, overexpression led to increased c-FLIPL Ht hypoxia-inducible factor 1 An overexpression of HIF-1 can up-regulation of genes that lead to global Ver Changes in cell proliferation, metastasis and invasion. In addition, overexpression of c-FLIP accelerated progression to Androgenunabh Dependence through the inhibition of apoptosis in LNCaP prostate tumors in mice Nacktm Implanted. Gathering information clearly shows that c-FLIP plays a role Middle finger in the development of resistance to death ligands and chemotherapeutic agents. Park et al. reported that MEK1 / 2 inhibitors interact synergistically with heat shock protein 90 inhibitor, hepatoma and pancreatic cancer in order to t th geldanamycins. Treatment of cells with MEK1 / 2 inhibitors and 17AAG reduced expression of c-flips was that the loss of MEK1 / 2 and AKT function is connected. In addition, the overexpression of c led flips or inhibition of caspase-8 abolished the Zellabt Tion by MEK1 / 2 inhibitors and 17AAG. ...
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We have examined a large panel of malignant glioma cell lines and identified TRAIL-sensitive and TRAIL-resistant cell lines (5, 7). TRAIL induces apoptosis in the sensitive cell lines through caspase-8-initiated extrinsic and intrinsic pathways (7). Caspase-8-initiated pathways, however, are inhibited in the resistant cell lines due to the recruitment of cellular Fas associate death domain-like IL-1β-converting enzyme-inhibitory protein (c-FLIP) and phosphoprotein enriched in astrocytes 15 kDa/(PEA-15)/phosphoprotein enriched in diabetes (PEA-15/PED) to the death-inducing signaling complex where they inhibit caspase-8 cleavage (46). Conventional chemotherapy agents, such as camptothecin, cisplatin, and etoposide, down-regulates c-FLIP and PED expression and thus sensitizes the resistant glioma cells to TRAIL-induced apoptosis (7). This combination treatment may prove to be effective in clinical treatment of malignant gliomas. In this study, however, we have identified two malignant glioma cell ...
Ezrin belongs to the ERM (ezrin-radixin-moesin) protein family and has been demonstrated to regulate early steps of Fas receptor signalling in lymphoid cells, but its contribution to TRAIL-induced cell death regulation in adherent cancer cells remains unknown. In this study we report that regulation of FasL and TRAIL-induced cell death by ezrin is cell type depen-dant. Ezrin is a positive regulator of apoptosis in T-lymphoma cell line Jurkat, but a negative regulator in colon cancer cells. Using ezrin phosphorylation or actin-binding mutants, we provide evidence that negative regulation of death receptor-induced apoptosis by ezrin occurs in a cytoskeleton-and DISC-independent manner, in colon cancer cells. Remarkably, inhibition of apoptosis induced by these ligands was found to be tightly associated with regulation of ezrin phosphorylation on serine 66, the tumor suppressor gene WWOX and activation of PKA. Deficiency in WWOX expression in the liver cancer SK-HEP1 or the pancreatic Mia PaCa-2 cell lines
Tumor Necrosis Apoptosis Inducing Ligand (TRAIL) is a death ligand with some specificity for transformed cells. However, some cancer cells develop resistance to TRAIL allowing escape from immune surveillance. Re-sensitization of these cells to TRAIL depends on identifying the mechanism of resistance and applying a targeted corrective. We studied several possible mechanisms of TRAIL resistance beginning with FLICE-Like Inhibitory Protein (FLIP). The short isoform of FLIP (FLIPshort) is an effective inhibitor of caspase 8 activation and therefore overexpression of FLIPshort may be a mechanism of TRAIL resistance. We found that downregulation of FLIP short was sufficient to re-sensitize some prostate carcinoma cells to TRAIL. Another mechanism we investigated is mediated by Elongation Factor 2 (EF2) which acilitates ribosomal translocation along mRNA strands. EF2 can be inactivated by phosphorylation or by ADP-ribosylation, thereby inhibiting protein synthesis. During inhibition of protein ...
Expression of CFLAR (c-FLIP, CASH, CASP8AP1, Casper, CLARP, FLAME, FLIP, I-FLICE, MRIT) in rectum tissue. Antibody staining with HPA019044, CAB022157 and CAB025216 in immunohistochemistry.
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Njv Athens Plaza Hotel is rated 5 stars and is placed about 1.6 km from National Archaeological Museum, Municipal Art Gallery and Museum Herakleidon. Residing in a 9-story building, the hotel was opened in 1980 and renovated in 2012.. The stylish hotel is placed in a business area, a short walk from a church, a theater and archaeological sites. The property lies within 1 km from the city center.. This hotel is conveniently placed close to restaurants, a stadium and cafés.. Guests are offered 180 soundproof hotel rooms equipped with a heating system, a balcony, a writing desk, multi-channel TV and an electronic safe. Some rooms feature a breathtaking view over the city. The rooms come with en suite bathrooms with a shower, toiletries and a Jacuzzi along with a small fridge, coffee/tea makers and an electric kettle.. Every morning at the bar guests may enjoy full American buffet breakfast. The Parliament restaurant makes fine dishes of Mediterranean cuisine from 08:00 to 23:30. The the ...
Molluscum contagiosum trojan (MCV) gene encodes a viral FLICE inhibitory proteins (vFLIP) that inhibits caspase-8-mediated apoptosis. contaminated cells and renewed MCMV duplication in macrophages partially. Nevertheless, MC159 do not really replace Meters45 completely, as it do not really slow down necroptosis in murine cells, but it decreased TNF-induced necroptosis in MCMV-infected individual HT-29 cells. MC159 differed from M45 in its effect on NF-B also. While MCMV-encoded Meters45 obstructed NF-B account activation by TNF- and interleukin-1 (IL-1), MC159 inhibited TNF- but not really IL-1-activated NF-B account activation in contaminated mouse fibroblasts. These outcomes indicate that the range of MC159t features differs depending on cell type and reflection program and that a cell lifestyle program for the distribution of MCV is normally required to determine the natural relevance of assumed virus-like gene features. IMPORTANCE 398493-79-3 MCV is a human-pathogenic poxvirus that cannot ...
Molluscum contagiosum trojan (MCV) gene encodes a viral FLICE inhibitory proteins (vFLIP) that inhibits caspase-8-mediated apoptosis. contaminated cells and renewed MCMV duplication in macrophages partially. Nevertheless, MC159 do not really replace Meters45 completely, as it do not really slow down necroptosis in murine cells, but it decreased TNF-induced necroptosis in MCMV-infected individual HT-29 cells. MC159 … Continue reading Molluscum contagiosum trojan (MCV) gene encodes a viral FLICE inhibitory proteins. ...
It is postulated that breast cancer stem cells (bCSCs) mediate disease recurrence and drive formation of distant metastases - the principal cause of mortality in breast cancer patients. Therapeutic targeting of bCSCs, however, is hampered by their heterogeneity and resistance to existing therapeutics. In order to identify strategies to selectively remove bCSCs from breast cancers, irrespective of their clinical subtype, we sought an apoptosis mechanism that would target bCSCs yet would not kill normal cells. Suppression of the apoptosis inhibitor cellular FLICE-Like Inhibitory Protein (c-FLIP) partially sensitizes breast cancer cells to the anti-cancer agent Tumour Necrosis Factor-Related Apoptosis Inducing Ligand (TRAIL). Here we demonstrate in breast cancer cell lines that bCSCs are exquisitely sensitive to the de-repression of this pro-apoptotic pathway, resulting in a dramatic reduction in experimental metastases and the loss of bCSC self-renewal. Suppression c-FLIP was performed by siRNA (FLIPi) in
TY - JOUR. T1 - Hypericin induced death receptor-mediated apoptosis in photoactivated tumor cells.. AU - Ali, Seyed Mohamed. AU - Chee, Soo Khee. AU - Yuen, Gan Yik. AU - Olivo, Malini. PY - 2002/6. Y1 - 2002/6. N2 - Nasopharyngeal carcinoma (NPC) is a malignant disease of the head/neck region with a 5-year survival level of approximately 65%. To explore the novel therapeutic strategies in the management of this disease, the potential effects of photodynamic therapy (PDT) in NPC cells were investigated. PDT, a new mode of treatment, is based on the combined use of light-absorbing compounds and light irradiation. Two human NPC cells such as, poorly differentiated (NPC/CNE2) and moderately differentiated (NPC/TW0-1) and other types of tumor cells like colon (CCL-220.1) and bladder (SD) undergo rapid apoptosis when treated with PDT sensitized with hypericin (HY). It has been shown that this compound has a strong photodynamic effect on tumors and viruses. However, the initiating events of PDT ...
Programmed cell death (apoptosis) is definitely a coordinated group of events eventually resulting in the substantial activation of specialised proteases (caspases) that cleave several substrates, orchestrating fairly standard biochemical shifts than culminate in mobile suicide. liberating cytochrome C from mitochondria. This is actually the stage of no come back in committing vertebrate cells to loss of life, as well as the aspartate where caspases cleave arrestin-2 is definitely evolutionary conserved in vertebrate, however, not in invertebrate arrestins. As opposed to wild-type arrestin-2, its caspase-resistant mutant will not facilitate cell loss of life. indicate immediate or indirect posttranslational activation; TNF receptor 1, receptor-interacting serine/threonine-protein 25332-39-2 supplier kinase 1, Fas-associated loss of life domain proteins, TNF receptor-associated loss of life domains (TRADD), TNF receptor-associated aspect, FLICE-like inhibitory proteins (a.k.a. CFLAR, CASP8, and ...
Thus, caspase-8 has a crucial pro-survival role in shutting off RIPK1 and preventing it from inducing necroptosis. But how, then, does a cell wherein caspase-8 is activated not die by apoptosis instead? How does it live to develop into a healthy mouse or human? Caspase-8 activates through dimerization; two molecules of caspase-8 are forcefully brought together to form an active complex. The previously mentioned adapter protein FADD is essential for initiating this process of dimerization, but recent evidence has shown that once a few dimers are formed around clusters of FADD, more caspase-8 dimers can form independent of FADD. An important clue comes from the observation that caspase-8 does not only activate when it dimerises with itself to form a homodimer, but can also when it forms a dimer with its cousin, FLIP (FLICE-like Inhibitory Protein), to form a heterodimer. FLIP is similar to caspase-8 but has no protease activity, it is an inactive caspase homologue. The heterodimer is active, but ...
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.
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Nonalcoholic steatohepatitis (NASH) is characterized by progressive liver injury, inflammation, and fibrosis; however, the mechanisms that govern the transition from hepatic steatosis, which is relatively benign, to NASH remain poorly defined. Neuregulin 4 (Nrg4) is an adipose tissue-enriched endocrine factor that elicits beneficial metabolic effects in obesity. Here, we show that Nrg4 is a key component of an endocrine checkpoint that preserves hepatocyte health and counters diet-induced NASH in mice. Nrg4 deficiency accelerated liver injury, fibrosis, inflammation, and cell death in a mouse model of NASH. In contrast, transgenic expression of Nrg4 in adipose tissue alleviated diet-induced NASH. Nrg4 attenuated hepatocyte death in a cell-autonomous manner by blocking ubiquitination and proteasomal degradation of c-FLIPL, a negative regulator of cell death. Adeno-associated virus-mediated (AAV-mediated) rescue of hepatic c-FLIPL expression in Nrg4-deficent mice functionally restored the brake ...
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RePosting SGP / iOptron CEM-60EC Meridian Flip Failure - posted in Mounts: I have another thread going on this enigma. I am posting again to possibly get new ideas as to the ongoing flip failure. I appreciate all the help in the other thread deeply...but it hasnt cured the problem. I am sitting at my pier with a bunch of daylight meridian targets ready to try anything before nightfall. Here is the log from the latest failure (only the flip failure section) and a link here to the oth...
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Expression of CFLAR (c-FLIP, CASH, CASP8AP1, Casper, CLARP, FLAME, FLIP, I-FLICE, MRIT) in ductus deferens tissue. Antibody staining with HPA019044, CAB022157 and CAB025216 in immunohistochemistry.
The protein c-FLIP figures prominently into how the body regulates this process. The protein exists as three different versions, or isoforms. While the roles of c-FLIP-L and c-FLIP-S isoforms are well established, until now relatively little has been known about the role of the c-FLIP-R isoform. Which is why Prof. Ingo Schmitz and the Braunschweig team of researchers decided to take a closer look at this particular isoform. What they found is that it confers protection on immune cells against the apoptosis program. If c-FLIP-R is activated, lymphocytes are apoptosis-resistant, says the head of the HZIs Systems-oriented Immunology and Inflammation Research work group, who also teaches at the OvGU. Apoptosis can take place only in the proteins absence ...
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... a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis". J. Biol. Chem. 272 (30): 18542-5. doi: ... Caspase-8 is a caspase protein, encoded by the CASP8 gene. It most likely acts upon caspase-3. CASP8 orthologs[5] have been ... protein complex binding. • scaffold protein binding. • protein binding. • identical protein binding. • cysteine-type ... The N-terminal FADD-like death effector domain of this protein suggests that it may interact with Fas-interacting protein FADD ...
... a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis". J. Biol. Chem. 272 (30): 18542-5. doi: ... Caspase-8 is a caspase protein, encoded by the CASP8 gene. It most likely acts upon caspase-3. CASP8 orthologs have been ... The N-terminal FADD-like death effector domain of this protein suggests that it may interact with Fas-interacting protein FADD ... "OrthoMaM phylogenetic marker: CASP8 coding sequence".[permanent dead link] "Entrez Gene: CASP8 caspase 8, apoptosis-related ...
This complex is called the TNFR-1 complex I. Complex-I is then modified by the IAPs (Inhibitor of Apoptosis Proteins) and the ... a protein complex known to regulate transcription of DNA and thus, related to survival processes. The best well-known pathway ... and DR4 induce FADD-dependent apoptosis and activate the NF-kappaB pathway". Immunity. 7 (6): 821-30. doi:10.1016/S1074-7613(00 ... RIPK1 has been shown to interact with: BIRC2, BIRC3, CA11, CASP8, CFLAR, CRADD, RIPK2, RIPK3, RNF11, RNF216, SQSTM1, TNFRSF1A, ...
... containing receptors and various signaling proteins. In addition, several viruses were recently shown … ... CASP8 and FADD-Like Apoptosis Regulating Protein * Carrier Proteins / metabolism * Carrier Proteins / physiology ... In addition, several viruses were recently shown to encode proteins with DEDs (also called FLICE inhibitory proteins or vFLIPs ... Modulation of the NF-kappa B pathway by virally encoded death effector domains-containing proteins Oncogene. 1999 Oct 14;18(42 ...
Here we show that loss of cIAPs promotes the spontaneous formation of an intracellular platform that activates either apoptosis ... CASP8 and FADD-Like Apoptosis Regulating Protein / metabolism * CASP8 and FADD-Like Apoptosis Regulating Protein / physiology* ... It contains RIP1, FADD, caspase-8, caspase-10, and caspase inhibitor cFLIP isoforms. cFLIP(L) prevents Ripoptosome formation, ... Here we show that loss of cIAPs promotes the spontaneous formation of an intracellular platform that activates either apoptosis ...
Can trigger apoptosis via FADD-mediated activation of CASP8. Plays a role in the regulation of the cytoskeleton by binding to ... Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa- ... In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at ... and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of ...
0 (CASP8 and FADD-Like Apoptosis Regulating Protein); 0 (DNA, Neoplasm). [Em] M s de entrada:. 1712. ... 0 (GNA11 protein, human); 0 (GTP-Binding Protein alpha Subunits); 0 (Membrane Proteins); EC (BRAF protein, human); EC ... Prote na Reguladora de Apoptosis Semelhante a CASP8 e FADD/gen tica. Neoplasias da T nica Conjuntiva/gen tica. DNA de ... Prote na Reguladora de Apoptosis Semelhante a CASP8 e FADD/metabolismo. Linhagem Celular Tumoral. Movimento Celular. Prolifera ...
casp8 and fadd-like apoptosis regulating protein (1) * cell culture techniques (1) ...
... and apoptosis, (e.g., CASP8, FADD, CTSS), and 16 were down-regulated including genes involved in the complement and coagulation ... 73 proteins were up-regulated. These included proteins involved in protein quality control in the endoplasmic reticulum, e.g., ... The 80 down-regulated proteins included the ribosomal proteins RPL3, RPS8, RPS5 and RPS18.. Conclusion. We developed an in- ... conidia (P-value , 0.05). Of the 56 genes, 40 were up-regulated including genes involved in rearrangement of actin cytoskeleton ...
Can trigger apoptosis via FADD-mediated activation of CASP8. Plays a role in the regulation of the cytoskeleton by binding to ... Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa- ... Gil J and Esteban M. Induction of apoptosis by the dsRNA-dependent protein kinase (PKR): Mechanism of action. Apoptosis 2000; 5 ... In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at ...
CASP8, and FADD-like apoptosis regulator (FLIP) but inactivates the proapoptotic protein Bad and caspase 9. Nonetheless, AMP- ... These proteins differ in their tissue distribution, and they are involved in regulating different biological processes such as ... P. Schwertman, A. Lagarou, D. H. W. Dekkers et al., "UV-sensitive syndrome protein UVSSA recruits USP7 to regulate ... Finally, PARylation, mediated by PARP1, regulates some of the NER proteins. First, DDB2 PARylation inhibits its ubiquitination ...
CASP8 and FADD-Like Apoptosis Regulating Protein * Ubiquitin * Colonic Neoplasms * Fever 18 Scopus citations ... Regulation of rad17 protein turnover unveils an impact of rad17-APC cascade in breast carcinogenesis and treatment. Zhou, Z., ... Interplay between arginine methylation and ubiquitylation regulates KLF4-mediated genome stability and carcinogenesis. Hu, D., ...
CASP8 and FADD-Like Apoptosis Regulating Protein * Death Domain Receptor Signaling Adaptor Proteins ... The SCFSkp2 ubiquitin ligase complex modulates TRAIL-R2-induced apoptosis by regulating FLIP(L). Roberts, J. Z., Holohan, C., ... R1095CEM: Klebsiella anti-immunology: exploiting proteins with a eukaryotic SEFIR domain. Bengoechea, J., Moynagh, P. & ...
Negatively regulates hypoxia-induced apoptosis in part by inhibiting the release of cytochrome c from mitochondria in a caspase ... dissociating its interaction with CASP8 and maintaining calcium homeostasis (PubMed:23382383). Negatively regulates oxidative ... Firstly by interacting with FAS and FADD upon FAS activation blocking death-inducing signaling complex (DISC) assembly (PubMed: ... Finally through its role as apoptosis repressor, promotes vascular remodeling through inhibition of apoptosis and stimulation ...
Death Domain Receptor Signaling Adaptor Proteins * CASP8 and FADD-Like Apoptosis Regulating Protein ... A revised model of TRAIL-R2 DISC assembly explains how FLIP(L) can inhibit or promote apoptosis. Humphreys, L. M., Fox, J. P., ...
CASP8 and FADD-Like Apoptosis Regulating Protein/genetics/metabolism ; Caspase 8/genetics/metabolism ; DNA Fragmentation/drug ... VPA induced apoptosis via the extrinsic pathway involving engagement of the caspase-8-dependent cascade. Although CLL cells are ... Valproic acid induces apoptosis in chronic lymphocytic leukemia cells through activation of the death receptor pathway and ... RESULTS: Exposure of CLL cells to VPA resulted in dose-dependent cytotoxicity and apoptosis in the 40 CLL patients. VPA ...
Transcripts for the protein FADD and the apoptosis regulatory protein Siva (SIVA1) were both downregulated during the ... upregulation was correlated with CASP8 expression (Fig. 4R). Activity of CDK1 is regulated by transcription and phosphorylation ... Apoptosis. Many genes involved in apoptosis were regulated in response to hypo-osmotic challenge, but gene ontology terms ... TNFα can also induce apoptosis by triggering activation of CASP8, and osmotic stress can induce TNFα-mediated apoptosis in ...
These include CASP8- and FADD-like apoptosis regulator (CASP8/CASPER/CLARP), caspase-10 (36, 37), and caspase-1, an interleukin ... a death effector domain-containing protein interacts with caspase-8 and regulates apoptosis. Proc. Natl. Acad. Sci. USA, 94: ... including death effector filament-forming Ced-4-like apoptosis protein, caspase recruitment domain protein 10, and apoptotic ... Shu, H. B., Halpin, D. R., and Goeddel, D. V. Casper is a FADD- and caspase-related inducer of apoptosis. Immunity, 6: 751-763 ...
... and down-regulated, respectively, in the MLCs of fish fed the diet with a lower level of fish oil, suggesting that they are ... Fatty acid-binding protein adipocyte (fabp4) and proteasome subunit beta type-8 (psmb8) were significantly up- ... The expression of the rnf8 (ring finger protein 8, E3 ubiquitin protein ligase) and cflar (CASP8 and FADD-like apoptosis ... casp8 and fadd-like apoptosis regulator), TNF (tumour necrosis factor), IL (interleukin), IFN (interferon), NEMO (NFKB1 ...
Viral Proteins/metabolism*. *fas Receptor/metabolism*. Substances. *CASP8 and FADD-Like Apoptosis Regulating Protein ... A viral FLIP (FLICE/caspase-8-Inhibitory Protein), equine herpesvirus type 2 E8 protein, has been shown to inhibit Death ... Although E8-expressing thymocytes were resistant to Fas-mediated apoptosis, the total number of thymocytes in 4-8-week-old E8 ... Thus, the Death receptor-mediated signaling pathway is too complex to be regarded as only an executor for apoptosis. ...
BIRC5 protein, human. *CASP8 and FADD-Like Apoptosis Regulating Protein. *CFLAR protein, human ... Protein kinases C (PKC) have been shown to be important in the regulation of proliferation and apoptosis. In this report, we ... PKCmu prevents CD95-mediated apoptosis and enhances proliferation in pancreatic tumour cells.. Trauzold A1, Schmiedel S, Sipos ... In an attempt to identify the signalling pathways affected by PKCmu, we identified the antiapoptotic proteins c-FLIPL and ...
CASP8 and FADD-Like Apoptosis Regulating Protein * Neoplasms * Apoptosis * Down-Regulation 22 Citations (Scopus) ... Vitamin D-binding protein enhances epithelial ovarian cancer progression by regulating the insulin-like growth factor-1/akt ... Role of placental fibrinogen-like protein 1 in gestational diabetes. Kang, L., Li, H. Y., Ou, H. Y., Wu, P., Wang, S. H., Chang ... Primary Cilium-Regulated EG-VEGF Signaling Facilitates Trophoblast Invasion. Wang, C. Y., Tsai, H. L., Syu, J. S., Chen, T. Y ...
CASP8 and FADD-Like Apoptosis Regulating Protein * Immediate-Early Proteins * Cytomegalovirus Retinitis ... Elevated SRPK1 lessens apoptosis in breast cancer cells through RBM4-regulated splicing events. Lin, J. C., Lin, C. Y., Tarn, W ... The impact of RNA binding motif protein 4-regulated splicing cascade on the progression and metabolism of colorectal cancer ... RBM4 down-regulates PTB and antagonizes its activity in muscle cell-specific alternative splicing. Lin, J. C. & Tarn, W. Y., 五月 ...
Dopamine and cAMP-Regulated Phosphoprotein 32 Stomach Neoplasms CASP8 and FADD-Like Apoptosis Regulating Protein ... The role of DARPP-32 in regulating TRAIL-dependent apoptosis was evaluated by clonogenic survival assay, Annexin V staining, ... The role of DARPP-32 in regulating TRAIL-dependent apoptosis was evaluated by clonogenic survival assay, Annexin V staining, ... The role of DARPP-32 in regulating TRAIL-dependent apoptosis was evaluated by clonogenic survival assay, Annexin V staining, ...
CASP8 and FADD-Like Apoptosis Regulating Protein * Apoptosis Regulatory Proteins * Drug Discovery ... Etoposide induces protein kinase Cδ- and caspase-3-dependent apoptosis in neuroblastoma cancer cells. Day, T. W., Wu, C. H. & ... c-FLIP knockdown induces ligand-independent DR5-, FADD-, caspase-8-, and caspase-9-dependent apoptosis in breast cancer cells. ... RNA interference in cancer: Targeting the anti-apoptotic protein c-FLIP for drug discovery. Day, T. W. & Safa, A. R., Sep 21 ...
CASP8 and FADD-Like Apoptosis Regulating Protein * Staphylococcal Protein A * Death Domain Receptor Signaling Adaptor Proteins ... Targeting the anti-apoptotic protein c-FLIP for cancer therapy. Safa, A. R. & Pollok, K. E., Jun 1 2011, In : Cancers. 3, 2, p ... Cellular FLICE-like inhibitory protein (C-FLIP): A novel target for cancer therapy. Safa, A. R., Day, T. W. & Wu, C. H., Feb 1 ... Role of post-translational modification of the Y box binding protein 1 in human cancers. Prabhu, L., Hartley, A. V., Martin, M ...
CASP8 and FADD-Like Apoptosis Regulating Protein * Apoptosis * Tumor Necrosis Factor-alpha ...
CASP8 and FADD-Like Apoptosis Regulating Protein * Proteasome Endopeptidase Complex * Vitamins * Pancreatic Neoplasms ... Arginase-1 expression in myeloid cells regulates Staphylococcus aureus planktonic but not biofilm infection. Yamada, K. J., ... Vitamin e δ-tocotrienol sensitizes human pancreatic cancer cells to TRAIL-induced apoptosis through proteasome-mediated down- ...
CASP8 and FADD-Like Apoptosis Regulating Protein. *Caspase 8. *Caspase 9. *Caspase Inhibitors ... Matrix attachment regulates Fas-induced apoptosis in endothelial cells: a role for c-flip and implications for anoikis. ... Matrix attachment regulates Fas-induced apoptosis in endothelial cells: a role for c-flip and implications for anoikis. ... Matrix attachment modulates Fas-mediated apoptosis at two different levels: by regulating the expression level of Fas, and by ...
CASP8 and FADD-Like Apoptosis Regulating Protein. CAT Enzyme use Chloramphenicol O-Acetyltransferase ... Calmodulin-Dependent Protein Kinase IV use Calcium-Calmodulin-Dependent Protein Kinase Type 4 ... Caspase and Rip Adaptor with Death Domain Protein use CRADD Signaling Adaptor Protein ... Ca(2+)-Calmodulin-Dependent Protein Kinase use Calcium-Calmodulin-Dependent Protein Kinases ...
Transport Proteins) are important in protein science because they carry specific substances in the blood and across cell ... Crk-Associated Substrate Protein *death domain receptor signaling adaptor proteins *CASP8 and FADD-like apoptosis regulating ... Carrier Proteins (Transport Proteins). "Carrier Proteins (Transport Proteins)" Transport Proteins (Carrier Proteins). In our ... "F-Box Proteins (F-Box Domain Proteins)" F-Box Protein Family. In our body, F-Box Proteins are a family of proteins that share ...
CASP8 and FADD-Like Apoptosis Regulating Protein * Neoplasms * Apoptosis * Down-Regulation 22 引文 斯高帕斯(Scopus) ... STK31 Is a Cell-Cycle Regulated Protein That Contributes to the Tumorigenicity of Epithelial Cancer Cells. Kuo, P-L., Huang, Y ... Functional antagonism between high temperature requirement protein a (HtrA) family members regulates trophoblast invasion. Chen ... Correlation between leucine rich domain and the stability of LRWD1 protein in human NT2/D1 cells. Tsai, Y. C., Teng, Y. N., ...
CASP8 and FADD-Like Apoptosis Regulating Protein (MeSH) * Caspase 8 (MeSH) * Cell Cycle Proteins (MeSH) ... positively and negatively regulating apoptosis, necroptosis, and inflammation. Here, we report an unanticipated cell-death- and ... Receptor-interacting protein kinase (RIPK) 1 functions as a key mediator of tissue homeostasis via formation of Caspase-8 ...
  • Interestingly, paxilline/TRAIL co-treatment did not induce apoptosis in normal astrocytes, nor did it affect the protein levels of CHOP, DR5 or survivin in these cells. (bvsalud.org)
  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered to induce apoptosis in a variety of cancer cells but not normal cells. (unboundmedicine.com)
  • Inhibition of RNA or proteins synthesis leading to the blockade of complicated I-mediated pro-survival NFB-mediated signaling must induce apoptosis via TNFR1 arousal generally in most cell types. (movd2016.org)
  • This report is designed to explore the molecular mechanism by which dihydroartemisinin (DHA) and ionizing radiation (IR) induce apoptosis in human lung adenocarcinoma A549 cells. (isharonline.org)
  • And apoptosis-inducing factor (AIF) , etc., activate the caspase cascade and induce apoptosis. (cusabio.com)
  • Overexpression of RIP can induce apoptosis and can activate NF-kB, but overexpression of the RIP death domain can block NF-kB activation by TNF-R1. (wikipedia.org)
  • Full length and shorter isoforms have been shown either to induce apoptosis or to reduce TNFRSF-triggered apoptosis. (genecards.org)
  • As a result, activated tumor-infiltrating lymphocytes can induce apoptosis of tumor cells ( 8 ). (frontiersin.org)
  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) of the tumor necrosis factor family ( 2 , 3 ) has been shown to induce apoptosis in malignant glioma cells in cultures and experimental animals ( 4 - 6 ) and thus is currently under development as a cancer therapeutic agent. (aacrjournals.org)
  • The anticancer activity of TRAIL is attributable to its ability to induce apoptosis through the binding of death receptors 4 and 5 (DR4, DR5) and the recruitment of intracellular apoptosis-initiating caspase-8 through Fas-associated death domain (FADD) for the assembly of a death-inducing signaling complex (DISC) ( 4 ). (aacrjournals.org)
  • Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding proinflammatory cytokines and IFNs. (uniprot.org)
  • CASP8, FADD, CTSS), and 16 were down-regulated including genes involved in the complement and coagulation cascades pathways (e.g. (aspergillus.org.uk)
  • In an attempt to identify the signalling pathways affected by PKCmu, we identified the antiapoptotic proteins c-FLIPL and survivin to be strongly upregulated in PKCmu overexpressing cells. (nih.gov)
  • In our body, GTP-Binding Proteins control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. (wellnessadvocate.com)
  • Overview of signal transduction pathways involved in apoptosis . (wikipedia.org)
  • Fas ligand (FasL) belongs to the TNF family of death ligands, and its binding to the FasR leads to activation of several downstream signaling pathways and proteins, including NF-κB and PI3K/Akt. (northwestern.edu)
  • During tumour progression, cancer cells use diverse mechanisms to escape from apoptosis-inducing stimuli, which may include receptor internalization, inhibition of signal pathways, and regulation of specific sets of genes. (elsevier.com)
  • A collection of articles that focus on an array of different scientific topics such as pathways, cancer, transmembrane proteins. (cusabio.com)
  • Among its related pathways are Apoptosis and survival Caspase cascade and CDK-mediated phosphorylation and removal of Cdc6. (cusabio.com)
  • Our bioinformatic analysis mapped these genes to differential molecular pathways that predict resistance and sensitivity of UACC903 and UACC903(+6) to apoptosis respectively. (pubmedcentralcanada.ca)
  • The pathways were functionally confirmed by the FAS ligand-induced cell death and by siRNA knockdown of BAK1 protein. (pubmedcentralcanada.ca)
  • These results demonstrated the differential molecular pathways underlying survival and apoptosis of UACC903 and UACC903(+6) cell lines. (pubmedcentralcanada.ca)
  • In this study, a Gene-Ontology driven global gene expression analysis coupled with protein abundance and activity assays identified genes and pathways associated with regulation of apoptosis in primary human CD3+ T cells and separately CD4+ and CD8+ T cells. (biomedcentral.com)
  • In this study we focus on the differentially expressed genes associated with regulation of apoptosis, as well as essential apoptotic signalling pathways: the NF-κB signalling pathway, and MAP kinase signalling. (biomedcentral.com)
  • What pathways are this gene/protein implicaed in? (cancerindex.org)
  • These results suggest that FADD and Daxx activate two independent pathways downstream of Fas and confirm the essential role of FADD binding in apoptosis induction. (pnas.org)
  • On Fas activation, Daxx interacts with and activates a mitogen-activated protein kinase kinase kinase termed ASK1 (Apoptosis Signal-regulating Kinase 1), leading to the activation of the Jun N-terminal kinase (JNK) and p38 MAP kinase pathways ( 22 ). (pnas.org)
  • Although genes involved in apoptosis pathways and DNA repair pathways are both essential for maintaining genomic integrity, genetic variants in DNA repair have been thought to increase susceptibility to radiation carcinogenesis, but similar hypotheses have not generally been raised about apoptosis genes. (cdc.gov)
  • Apoptosis, the first genetically programmed death process identified, is a cellintrinsic mechanism for suicide that is regulated by a variety of cellular signaling pathways. (cusabio.com)
  • Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions in a variety of cellular pathways related to both cell survival and death. (wikipedia.org)
  • It has been shown that cell survival can be regulated through different RIPK1-mediated pathways that ultimately result in the expression of NF-kB, a protein complex known to regulate transcription of DNA and thus, related to survival processes. (wikipedia.org)
  • Our results indicate that the bacteria block apoptosis at multiple checkpoints along both pathways so that even if a cell fails to prevent apoptosis at an early step, Shigella will block apoptosis at the level of caspase-3. (biomedcentral.com)
  • Apoptosis regulator protein which may function as a crucial link between cell survival and cell death pathways in mammalian cells. (genecards.org)
  • There are two dominant apoptosis-related signaling pathways: the Fas/Fas ligand (FasL) mediated ligand-binding external pathway and the mitochondrial dependent internal pathway ( 7 ). (frontiersin.org)
  • Serine-threonine kinase which is a key regulator of TNF -mediated apoptosis, necroptosis and inflammatory pathways (PubMed:25459879, PubMed:31827281, PubMed:31827280). (rcsb.org)
  • TRAIL induces apoptosis through both receptor-mediated extrinsic and mitochondria-involved intrinsic pathways ( 11 ). (aacrjournals.org)
  • Death Effector Domains (DEDs) have been known to mediate the recruitment of Caspase 8 and its homologs to the aggregated death-inducing signaling complex (DISC), consisting of the death domain (DD)-containing receptors and various signaling proteins. (nih.gov)
  • In addition, several viruses were recently shown to encode proteins with DEDs (also called FLICE inhibitory proteins or vFLIPs) which have the ability of blocking cell death induced by DD-containing receptors. (nih.gov)
  • In addition, this compound did not regulate the death-inducing receptors DR4 and DR5. (bvsalud.org)
  • Exposure to LAQ824 increased the mRNA and protein expressions of the death receptors DR5 and/or DR4, but reduced the mRNA and protein levels of cellular FLICE-inhibitory protein (c-FLIP). (unboundmedicine.com)
  • This domain interacts with other DD-containing proteins and couples the death receptors to caspase activation and apoptosis. (wikipathways.org)
  • Intracellular signaling peptides and proteins that bind directly or indirectly to the cytoplasmic portion of TUMOR NECROSIS FACTOR RECEPTORS. (harvard.edu)
  • Intracellular signaling adaptor proteins that bind to the cytoplasmic death domain region found on DEATH DOMAIN RECEPTORS. (umassmed.edu)
  • Many of the proteins in this class take part in intracellular signaling from TUMOR NECROSIS FACTOR RECEPTORS. (umassmed.edu)
  • We identified significantly regulated apoptotic genes in several protein families, such as BCL2 proteins, CASPASE proteins, and TNF receptors, and detailed their transcriptional kinetics during the T-cell activation process. (biomedcentral.com)
  • Members of the tumor necrosis factor receptor (TNFR) superfamily are cell surface cytokine receptors that control critical cell fate decisions such as proliferation, differentiation, and apoptosis. (pnas.org)
  • The death domain is homologous to the DD of other receptors such as Fas, TRAILR2 (DR5), TNFR1 and TRAILR1 (DR4), so it can bind to these receptors, as well as TRADD and FADD in the TNFR1 signalling complex. (wikipedia.org)
  • FADD is a common adaptor shared by several death receptors for signalling apoptosis through recruitment and activation of caspase 8 (refs 1-3). (jefferson.edu)
  • Cellular FLICE-inhibitory protein (c-FLIP) could inhibit apoptosis directly at the death-inducing signaling complex of death receptors and is also considered to be the main cause of immune escape. (frontiersin.org)
  • Cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein (c-FLIP) is a key anti-apoptotic regulator that inhibits cell death mediated by the death receptors Fas, DR4, DR5, and TNF-R1 ( 9 ). (frontiersin.org)
  • Activation of TLRs or receptors for proinflammatory cytokines (including IL-1β per se) induces the NF-κB-dependent expression of proIL-1β (33 kDa) as a cytosolic, biologically inactive precursor protein. (jimmunol.org)
  • Inhibits viral replication via phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (EIF2S1), this phosphorylation impairs the recycling of EIF2S1 between successive rounds of initiation leading to inhibition of translation which eventually results in shutdown of cellular and viral protein synthesis. (uniprot.org)
  • Inhibition of TLR9 by small interfering (si) RNA or an inhibitor suppressed CpG ODN-mediated anti-apoptosis. (bvsalud.org)
  • Inhibition of PKCmu with Goe6983 sensitized resistant cells to CD95-induced apoptosis. (nih.gov)
  • We further show that detachment-induced cell death, or anoikis, itself results from activation of the Fas pathway by its ligand, Fas-L. Fas-L/Fas interaction, Fas-FADD complex formation, and caspase-8 activation precede the bulk of anoikis in endothelial cells, and inhibition of any of these events blocks anoikis. (nih.gov)
  • Finally through its role as apoptosis repressor, promotes vascular remodeling through inhibition of apoptosis and stimulation of proliferation, in response to hypoxia (By similarity). (uniprot.org)
  • Cellular FLICE-inhibitory protein (c-FLIP), an antioxidant and an important component of the death-inducing signaling complex, also represses NF-κB upstream of the regulatory IκB kinase-γ protein subunit in the NF-κB signaling pathway, and positive cross-talk exists between Akt and c-FLIP in the context of inhibition of FasL-induced NF-κB activity. (northwestern.edu)
  • Partial inhibition of apoptosis due to LAQ824 or Apo-2L/TRAIL exerted by Bcl-2 overexpression was reversed by cotreatment with LAQ824 and Apo-2L/TRAIL. (unboundmedicine.com)
  • Inhibition of Fas-mediated apoptosis by the B cell antigen receptor through c-FLIP. (naver.com)
  • Fas ligand-induced apoptosis is regulated by nitric oxide through the inhibition of fas receptor clustering and the nitrosylation of protein kinase Cepsilon. (semanticscholar.org)
  • This occurred through a low-density lipoprotein receptor-related protein 1 (LRP1) dependent mechanism, as LRP1 inhibition significantly reduced uptake. (ubc.ca)
  • The goal of this research was to identify host factors that contribute to apoptosis inhibition in infected cells. (biomedcentral.com)
  • Compared to uninfected cells, Shigella- infected epithelial cells, both in the presence and absence of staurosporine, showed significant induced expression of JUN , several members of the inhibitor of apoptosis gene family, nuclear factor κB and related genes, genes involving tumor protein 53 and the retinoblastoma protein, and surprisingly, genes important for the inhibition of the extrinsic pathway of apoptosis. (biomedcentral.com)
  • Infection of epithelial cells with S. flexneri induces a pro-survival state in the cell that results in apoptosis inhibition in the presence and absence of staurosporine. (biomedcentral.com)
  • Apoptosis inhibition is most likely vital to the survival of the bacteria in vivo . (biomedcentral.com)
  • We previously observed that probiotic bacteria could prevent inhibition of lymphoproliferation and apoptosis responses of T cells associated with S. enterica infections in orally challenged mice. (beds.ac.uk)
  • In the cytosol, Smac interacts with X-linked inhibitor of apoptosis protein to release its inhibition of caspase-3 ( 17 ). (aacrjournals.org)
  • Specific inhibition of the expression of these two transcription factors was shown to increase apoptosis induced by chemotherapeutic agents under hypoxia indicating an involvement of HIF-1 and AP-1 in the anti-apoptotic effect of hypoxia. (biomedcentral.com)
  • After HIF-1 specific inhibition and using TaqMan Human Apoptosis Array, 8 potential HIF-1 target genes were identified which could take part in this protection. (biomedcentral.com)
  • These results identify A20 E3 ligase as a therapeutic target whose inhibition can overcome TNF-related apoptosis-inducing ligand resistance in glioblastoma and thus have an impact on ongoing clinical trials of TNF-related apoptosis-inducing ligand-targeted combination cancer therapies. (aacrjournals.org)
  • TRADD, which acts as a scaffold protein, recruits TRAF2 and RIPK1 to form a complex , referred to as complex 1. (wikipathways.org)
  • In some cases, FADD/CASP8 association depends on high molecular weight complexes containing unubiquitinated RIPK1 as scaffold. (wikipathways.org)
  • On TNF stimulation, deubiquitinated RIPK1 dissociates from complex 1 and recruits RIPK3, FADD and CASP8. (wikipathways.org)
  • Recruitment of CASP8, activation of FADD/RIP1 and apoptosis induction, is blunted when RIPK1 becomes ubiquitinated. (wikipathways.org)
  • Cellular inhibitor of apoptosis, BIRC2 and BIRC3 has E3-ubiquitin ligase activity and functionally interact with TRAF2 and RIPK1 to induce polyubiquitination of RIPK1 upon TNF stimulation. (wikipathways.org)
  • The adaptor proteins TAB2 and TAB3 bind preferentially to Lys-63 polyubiquitinated RIPK1. (wikipathways.org)
  • Initiates ripoptocide which describes cell death that is dependent on RIPK1, be it apoptosis or necroptosis (PubMed:31457011). (icr.ac.uk)
  • Upon binding of TNF to TNFR1, RIPK1 is recruited to the TNF-R1 signaling complex (TNF-RSC also known as complex I) where it acts as a scaffold protein promoting cell survival, in part, by activating the canonical NF-kB pathway (By similarity). (icr.ac.uk)
  • Specific conditions can however activate RIPK1, and its kinase activity then regulates assembly of two death-inducing complexes, namely complex IIa (RIPK1-FADD-CASP8) and the complex IIb (RIPK1-RIPK3-MLKL) and these complexes respectively drive apoptosis or necroptosis, a regulated form of necrosis (PubMed:19524513, PubMed:19524512, PubMed:29440439, PubMed:30988283). (icr.ac.uk)
  • Component of complex IIa composed of at least RIPK1, FADD and CASP8 (By similarity). (icr.ac.uk)
  • Also regulates apoptosis: apoptosis depends on RIPK1 , FADD and CASP8 , and is independent of MLKL and RIPK3 kinase activity (PubMed:27321907). (sdsc.edu)
  • Cleaves RIPK1 at 'Asp-325', which is crucial to inhibit RIPK1 kinase activity, limiting TNF -induced apoptosis, necroptosis and inflammatory response (PubMed:31511692). (sdsc.edu)
  • In terms of cell death, RIPK1 plays a role in apoptosis and necroptosis. (wikipedia.org)
  • This protein belongs to the Receptor Interacting Protein (RIP) kinases family, which consists of 7 members, RIPK1 being the first member of the family. (wikipedia.org)
  • RIPK1 protein is composed of 671 amino acids, and has a molecular weight of about 76 kDa. (wikipedia.org)
  • Kinase activity of RIPK1 is also required for RIPK1-dependent apoptosis in conditions of IAP1/2 depletion, TAK1inhibition/depletion, RIPK3 depletion or MLKL depletion. (wikipedia.org)
  • While being in complex I, RIPK1 has also been proved to play a role in the activation of MAP (mitogen-activated protein) kinases such as JNK, ERK and p38. (wikipedia.org)
  • A pro-apoptotic complex is created while RIPK1 also mediates the interaction between PIDD, NEMO and IKK subunits that will eventually result in the IKK complex activation after interaction with ATM kinase (a DNA double-strand breaks stimulated protein). (wikipedia.org)
  • FADD could directly bind to RIP1 (also known as RIPK1), a serine/threonine kinase that mediates both necrosis and NF-κB activation. (jefferson.edu)
  • Consistently, Ripk1 D325A/D325A and Ripk1 D325A /+ cells were hypersensitive to RIPK3-dependent TNF-induced apoptosis and necroptosis. (nature.com)
  • MK2 phosphorylation of RIPK1 regulates TNF-mediated cell death. (nature.com)
  • Death Domain Receptor Signaling Adaptor Proteins" 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 "Death Domain Receptor Signaling Adaptor Proteins" by people in this website by year, and whether "Death Domain Receptor Signaling Adaptor Proteins" was a major or minor topic of these publications. (umassmed.edu)
  • Below are the most recent publications written about "Death Domain Receptor Signaling Adaptor Proteins" by people in Profiles. (umassmed.edu)
  • To activate IKK, TAB2 and TAB3 adaptor proteins recruit TAK1 or MEKK3, which phosphorylate the complex. (wikipedia.org)
  • We provide evidence that vFLIPs can also modulate the NF-kappaB pathway and physically interact with several signaling proteins, such as the TRAFs, RIP, NIK and the IKKs. (nih.gov)
  • Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6. (uniprot.org)
  • Valproic acid induces apoptosis in chronic lymphocytic leukemia cells through activation of the death receptor pathway and potentiates TRAIL response. (uliege.be)
  • en] OBJECTIVE: Chronic lymphocytic leukemia (CLL) cells develop chemoresistance over time associated with defects in apoptosis pathway. (uliege.be)
  • VPA induced apoptosis via the extrinsic pathway involving engagement of the caspase-8-dependent cascade. (uliege.be)
  • Taken together, these results show that paxilline effectively sensitizes glioma cells to TRAIL-mediated apoptosis by modulating multiple components of the death receptor-mediated apoptotic pathway. (bvsalud.org)
  • CpG ODN-mediated anti-apoptosis depended on the TLR9-Akt-FoxO3a signaling pathway. (bvsalud.org)
  • Thus, the Death receptor-mediated signaling pathway is too complex to be regarded as only an executor for apoptosis. (nih.gov)
  • This suggests that upregulation of BCL-xL could play a possible role in blocking the mitochondria intrinsic apoptosis pathway, whereas the DARPP-32 effect on the NF-κB/FLIP(S) axis could serve as an additional negative feedback loop that blocks TRAIL-induced activation of caspase-8. (elsevier.com)
  • Conclusion: Our findings uncover a novel mechanism of TRAIL resistance mediated by DARPP-32, whereby it inhibits the intrinsic apoptosis pathway through upregulation of BCL-xL, and the extrinsic apoptosis pathway through the NF-κB/FLIP(S) axis. (elsevier.com)
  • The extracellular signal-regulated kinase (Erk) cascade functions as a survival pathway in adherent cells by regulating c-Flip expression. (nih.gov)
  • For the death pathway, the caspase-8 zymogen is cleaved into subunits that assemble to form the mature, highly active caspase heterotetramer whereas for the activation pathway, the zymogen appears to remain intact perhaps to limit its proteolytic function but enhance its capability as an adapter protein. (wikipedia.org)
  • Both CD95 and FADD immunoprecipitates were analyzed by Western blotting using monoclonal or polyclonal Abs directed against the components of the DISC (CD95, FADD, and caspase-8) or against the natural antagonist of the death receptor signaling pathway c-FLIP. (nih.gov)
  • Examination of genes involved in MAP kinase signalling pathway, important in apoptosis, suggests an induction of p38 and ERK1 cascades in T-cell proliferation (at 48 to 96 hours), which was explored using phosphorylation assays for p38 (MAPK14) and ERK1 (MAPK3). (biomedcentral.com)
  • Here we show that FADD, which couples Fas to pro-caspase-8, and, Daxx, which couples Fas to the Jun N-terminal kinase pathway, bind independently to the Fas death domain. (pnas.org)
  • An alternate pathway involves the Fas-binding protein Daxx ( 21 ). (pnas.org)
  • The main signaling pathway of apoptosis is the mitochondrial pathway and the death receptor pathway. (cusabio.com)
  • Intracellular apoptosis signals usually activate the mitochondrial pathway, stimulate the activation of BH3-only protein to bind to apoptotic proteins such as Bcl-2 , activate Bax/Bak aggregation to the mitochondrial membrane, and release mitochondrial pro-apoptotic proteins including cytochrome C , SMAC/DIABLO. (cusabio.com)
  • On one hand, it can serve as a cell survival pathway by suppressing apoptosis, for example, the removal of damaged organelles that are a source of genotoxic ROS, or by catabolizing cellular macromolecules to provide a source of nutrients and energy for the starved cell, or by limiting ER stress through the degradation of unfolded protein aggregates. (cusabio.com)
  • In the clinical trial of arsenic trioxide treatment of T lymphocytes, it was also found that both were activated simultaneously [4] , and the antibacterial drug chloroiodoquinoline induced autophagic death and apoptosis in leukemia cells and myeloma cells by disrupting the mTOR signaling pathway [5] . (cusabio.com)
  • In order to understand the pro-survival effects induced by the bacteria, we utilized apoptosis-specific microarrays to analyze the changes in eukaryotic gene expression in both infected and uninfected cells in the presence and absence of staurosporine, a chemical inducer of the intrinsic pathway of apoptosis. (biomedcentral.com)
  • The probiotic bacteria were also associated with reduced mRNA expression of a group of genes ( RelB, Myd88, I κκ a, Jun, Irak2 ) related to nuclear factor of kappa light chains enhancer in B cells (NF-κB) signal transduction pathway-regulated cytokine responses. (beds.ac.uk)
  • Caspases are involved in the signaling pathway that directs programmed cell death (apoptosis) in activated immune cells. (beds.ac.uk)
  • T cells that have been activated, but lacking secondary signals, activate an intrinsic caspase pathway that is arrested by signals from B- cell CLL/lymphoma 2 (BCL) 2 and its related proteins. (beds.ac.uk)
  • The canonical cleavage and processing of proIL-1β into mature IL-1β cytokine (17 kDa) are catalyzed by caspase-1, a pathway regulated by multiprotein inflammasome signaling complexes. (jimmunol.org)
  • The TNF-related apoptosis-inducing ligand (TRAIL) apoptotic pathway has emerged as a therapeutic target for the treatment of cancer. (aacrjournals.org)
  • Cell attachment to extracellular matrix inhibits apoptosis in endothelial cells both in vitro and in vivo, but the molecular mechanisms underlying matrix-induced survival signals or detachment-induced apoptotic signals are unknown. (nih.gov)
  • This protein is involved in the programmed cell death induced by Fas and various apoptotic stimuli. (wikipedia.org)
  • CASP8 activates apoptotic signal through another mechanism involving BID cleavage to truncated BID (tBID). (wikipathways.org)
  • On complex 1 formation, NF-κB regulated anti-apoptotic gene products efficiently block initiation of apoptosis by complex 2. (wikipathways.org)
  • However, the regulation of apoptosis and the balance between the anti-apoptotic and pro-apoptotic signalling (which is an essential part of the surveillance machinery) during the process of T-cell activation have not been examined. (biomedcentral.com)
  • We identified several potentially important apoptotic genes based on their patterns of expression and examined the protein expression of a select set of genes, most of which have not been previously discussed in T-cell activation. (biomedcentral.com)
  • Smac is normally a proteins released in the mitochondria as well as cytochrome C that interacts with and inhibits apoptotic inhibitors XIAP, cIAP1, and cIAP2 (Chai et al. (movd2016.org)
  • the third one is that autophagy acts as enabler of apoptosis, participating in certain morphologic and cellular events that occur during apoptotic cell death, without leading to death in itself [2] . (cusabio.com)
  • Altogether, these data highlight two mechanisms by which hypoxia could mediate its protective role via the activation of two transcription factors and, consecutively, changes in gene expression encoding different anti- and pro-apoptotic proteins. (biomedcentral.com)
  • Reference : Valproic acid induces apoptosis in chronic lymphocytic leukemia cells through activat. (uliege.be)
  • Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) induces apoptosis selectively in cancer cells while sparing normal cells. (bvsalud.org)
  • Activated CASP8 induces CASP3 activity and execution of apoptosis. (wikipathways.org)
  • Ceramide induces membrane permeabilization and apoptosis. (wikipathways.org)
  • Depending on the signal from the B cell antigen receptor, Fas induces either apoptosis or proliferation of B cells in vivo ( 5 ). (pnas.org)
  • Morgan M, Thorburn J, Pandolfi PP, Thorburn A. Nuclear and cytoplasmic shuttling of TRADD induces apoptosis via different mechanisms. (ucdenver.edu)
  • induces growth arrest or apoptosis depending on the physiological circumstances and cell type. (string-db.org)
  • Acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. (string-db.org)
  • Auf www.antikoerper-online.de finden Sie aktuell 434 Caspase 8, Apoptosis-Related Cysteine Peptidase (CASP8) Antikörper von 38 unterschiedlichen Herstellern. (antikoerper-online.de)
  • On www.antibodies-online.com are 406 Caspase 8, Apoptosis-Related Cysteine Peptidase (CASP8) Antibodies from 37 different suppliers available. (antibodies-online.com)
  • LIMMA (R package) was used to identify differentially abundant genes and proteins. (aspergillus.org.uk)
  • Of the 56 genes, 40 were up-regulated including genes involved in rearrangement of actin cytoskeleton (e.g. (aspergillus.org.uk)
  • NanoString and shotgun proteomics identified key candidate genes and proteins involved in the early host response to conidia. (aspergillus.org.uk)
  • Genes involved in cell volume regulation, nucleosome maintenance, ion transport, energetics, mitochondrion function, transcriptional regulation and apoptosis showed population- and salinity-dependent patterns of expression during acclimation. (biologists.org)
  • Transcriptional patterns of a few select genes (BCL2A1, BBC3 and CASP3) were validated at the protein level. (biomedcentral.com)
  • Upregulation of NF-κB and IκB family genes (REL, RELA, and RELB, NFKBIA, NFKBIE and NFKB1) at 48 to 96 hours, supported by the increase of phosphorylated RELA (p65), suggests that the involvement of the NF-κB complex in the process of T-cell proliferation is not only regulated at the protein level but also at the transcriptional level. (biomedcentral.com)
  • This comparative genome-scale, transcriptional analysis of T-cell activation in the CD4+ and CD8+ subsets and the mixed CD3+ population identified many apoptosis genes not previously identified in the context of T-cell activation. (biomedcentral.com)
  • Recruitment from the IKK complicated leads towards the phosphorylation from the NFB inhibitory proteins IB, using its following degradation, and activation 25332-39-2 supplier of NFB-dependent transcription of antiapoptotic genes such as for example cFLIP, cIAP1, cIAP2, BCL-XL, and XIAP (Kreuz et al. (movd2016.org)
  • Exogenous addition of HepL to rat cardiomyocytes produced a dramatically altered expression of apoptosis-related genes, and protection against HG and H₂O₂ induced cell death. (ubc.ca)
  • Polymorphisms in apoptosis- and proliferation-related genes, ionizing radiation exposure, and risk of breast cancer among U.S. Radiologic Technolog. (cdc.gov)
  • In a case-control study of 859 cases and 1,083 controls within the U.S. Radiologic Technologists cohort, we assessed breast cancer risk with respect to 16 candidate variants in eight genes involved in apoptosis, inflammation, and proliferation. (cdc.gov)
  • Secretion of these proteins is dependent on a type III secretion system (T3SS), which is encoded by 20 genes in the mxi-spa locus of the virulence plasmid. (biomedcentral.com)
  • Percentage of genes up-regulated (gray bars) and down-regulated (open bars) ≥1.5-fold were grouped into ( A ) functional categories/ontologies or ( B ) ontologies involved in inflammation using Spotfire DecisionSite software based on the Gene Ontology Consortium database. (jimmunol.org)
  • Total genes up-regulated and down-regulated in each grouping are represented within the bar. (jimmunol.org)
  • Percentages represent genes that were up-regulated following infection. (jimmunol.org)
  • Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. (string-db.org)
  • Probiotic bacteria increased expression of mRNA for clusters of differentiation antigen 2 ( Cd2 ), protein tyrosine phosphatase receptor type C ( Ptprc ), and Toll-like receptor 6 ( Tlr6 ) genes related to T and B cell activation in mouse intestinal tissue. (beds.ac.uk)
  • CGH detected loss of the chromosomal regions that contain the following genes: 8p12-p23 ( DR4 and DR5 ), 2q33-34 ( caspase-8 ), 11q13.3 ( FADD ), 22q11.2 ( Bid ), and 12q24.1-q24.3 ( Smac / DIABLO ) in TRAIL-resistant cell lines. (aacrjournals.org)
  • Caspase-8 is a caspase protein, encoded by the CASP8 gene. (wikipedia.org)
  • The CASP8 gene encodes a member of the cysteine - aspartic acid protease ( caspase ) family. (wikipedia.org)
  • CFLAR (CASP8 And FADD Like Apoptosis Regulator) is a Protein Coding gene. (cusabio.com)
  • An important paralog of this gene is CASP8. (cusabio.com)
  • What does this gene/protein do? (cancerindex.org)
  • For this reason, potential modification of the relationship between ionizing radiation exposure and breast cancer risk by polymorphic apoptosis gene variants have not been investigated among radiation-exposed women. (cdc.gov)
  • The protein encoded by this gene is a regulator of apoptosis and is structurally similar to caspase-8. (genecards.org)
  • CASP8 (Caspase 8) is a Protein Coding gene. (genecards.org)
  • Gene Ontology (GO) annotations related to this gene include protein heterodimerization activity . (genecards.org)
  • The protein encoded by this gene is a member of the TNF-receptor superfamily. (avivasysbio.com)
  • The responses were temporally correlated with downregulation of cellular inhibitor of apoptosis protein 1, suggesting suppressive roles for this and likely other inhibitor of apoptosis proteins on the stability and/or proteolytic activity of the caspase-8 platforms. (jimmunol.org)
  • IFN-induced dsRNA-dependent serine/threonine-protein kinase which plays a key role in the innate immune response to viral infection and is also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation. (uniprot.org)
  • Several proteins that can bind to the cytoplasmic death domain of Fas have been implicated in Fas signal transduction. (pnas.org)
  • Moreover, mitochondria play a key role in the signal transduction cascades that precipitate many (but not all) regulated variants of cellular demise. (microbialcell.com)
  • CFLAR, short for CASP8 and FADD-like apoptosis regulator, is also known as cellular FLICE--like inhibitory protein (c-FLIP). (cusabio.com)
  • Three additional independent signals from intronic SNPs were identified, in CASP8 (rs36043647), ALS2CR11 (rs59278883) and CFLAR (rs7558475). (ox.ac.uk)
  • CFLAR, CASP8, and FADD-like apoptosis regulator), loss of life domain, loss of life effector domains, receptor tyrosine kinase, G protein-coupled receptor Arousal of TNFR1 and very similar DR leads to the forming of two signaling complexes. (movd2016.org)
  • In this study, we describe a previously unidentified allele of caspase 8- and FADD-like apoptosis regulator ( Cflar ) (encoding cFLIP) that makes mice of MSM strain resistant to Fas-mediated lethality. (pnas.org)
  • Linkage analysis in F2 intercross (B6 x MSM) progeny identified several MSM loci controlling resistance to Fas-mediated death, including the caspase 8- and FADD-like apoptosis regulator ( Cflar ) locus encoding cFLIP. (pnas.org)
  • Blockade of NFB signaling promotes TNFR1-induced apoptosis mainly by blocking the formation of cFLIP that inhibits caspase-8 activation (Kreuz et al. (movd2016.org)
  • Phosphorylation on Ser-387 during mitosis by CDK1 inhibits activation by proteolysis and prevents apoptosis. (abcam.com)
  • Shigella flexneri inhibits apoptosis in infected epithelial cells. (biomedcentral.com)
  • Future characterization of these host factors is required to fully understand how S. flexneri inhibits apoptosis in epithelial cells. (biomedcentral.com)
  • However, malignant glioma cells express X-linked inhibitor of apoptosis protein ( 16 ) that interacts with caspase-3 and inhibits caspase-8 cleavage of caspase-3 ( 17 ). (aacrjournals.org)
  • We show that A20-mediated ubiquitination inhibits caspase-8 cleavage and TRAIL-induced apoptosis in glioblastoma through 2 signaling complexes. (aacrjournals.org)
  • These death-responsive cells show prolonged TNF stimulation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase, but no NF-κB transcriptional activity as a consequence of receptor-interacting protein degradation by caspases. (strath.ac.uk)
  • Conversely, cells of a proliferative phenotype display antiapoptotic NF-κB responses that antagonize c-Jun N-terminal kinase and p38 mitogen-activated protein kinase stress kinase effects. (strath.ac.uk)
  • Here we show that loss of cIAPs promotes the spontaneous formation of an intracellular platform that activates either apoptosis or necroptosis. (nih.gov)
  • Negatively regulates ISP by inducing the inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at 'Ser-312' and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of insulin receptor substrate 2 (IRS2). (uniprot.org)
  • TRAF-2 in complex 1 also activates the MAP kinase cascade, that leads to the activation of JNK, which on prolonged activation is believed to mediate both apoptosis and necrotic cell death. (wikipathways.org)
  • Serine/threonine-protein kinase that activates necroptosis and apoptosis, two parallel forms of cell death (PubMed:27321907, PubMed:27746097, PubMed:27917412, PubMed:28607035, PubMed:32200799, PubMed:32296175). (sdsc.edu)
  • Bender LM, Morgan MJ, Thomas LR, Liu ZG, Thorburn A. The adaptor protein TRADD activates distinct mechanisms of apoptosis from the nucleus and the cytoplasm. (ucdenver.edu)
  • Purpose: We previously found that cellular FLICE-inhibitory protein (c-FLIP), caspase 8, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor 2 (DR5) are major regulators of cell viability and chemotherapy-induced apoptosis in colorectal cancer. (qub.ac.uk)
  • On the other hand, kurarinone significantly inhibited TRAIL-induced IKK activation, IkappaB degradation and nuclear translocation of NF-kappaB, as well as effectively suppressed cellular FLICE-inhibitory protein long form (cFLIPL) expression. (bvsalud.org)
  • In addition, paxilline treatment markedly downregulated the protein levels of the short form of the cellular FLICE-inhibitory protein (c-FLIPS) and the caspase inhibitor, survivin, through proteasome-mediated degradation. (bvsalud.org)
  • Stimulation of macrophages with TLR9 agonist prevented apoptosis induced by serum deprivation through increased expression of FLICE-like inhibitory protein (FLIP). (bvsalud.org)
  • Reduction of thymocyte numbers in transgenic mice expressing viral FLICE-inhibitory protein in a Fas-independent manner. (nih.gov)
  • A viral FLIP (FLICE/caspase-8-Inhibitory Protein), equine herpesvirus type 2 E8 protein, has been shown to inhibit Death receptor-induced apoptosis by suppressing the activation of FLICE/caspase-8. (nih.gov)
  • These proliferative effects of TNF are apparently due to enhanced basal expression of the caspase-8/FLICE-inhibitory protein FLIP. (strath.ac.uk)
  • Recently, cellular FLICE-like inhibitory protein (cFLIP) has been identified as an endogenous inhibitor of Fas- or other receptor-mediated apoptosis and its altered high expression has a suspected association with tumour development or progression. (elsevier.com)
  • As the mammalian homolog of v-FLIP (virus FLICE-like inhibitory protein), c-FLIP is structurally and sequentially homologous with caspase-8 and caspase-10 that are involved in the initiation of DR (death receptor)-induced apoptosis. (cusabio.com)
  • Binding of TNFα to TNF-R1 on the cell surface triggers trimerization of the receptor and exposes intracellular domain of TNF-R1 following the release of an inhibitory protein. (wikipathways.org)
  • FLICE-inhibitory protein is a key regulator of germinal center B cell apoptosis. (nih.gov)
  • We found that GC B cells ex vivo display a preformed inactive DISC containing Fas-associated death domain-containing protein (FADD), procaspase-8, and the long isoform of cellular FADD-like IL-1beta-converting enzyme-inhibitory protein (c-FLIP(L)) but not the CD95L. (nih.gov)
  • Likely target for the cowpox virus CRMA death inhibitory protein. (abcam.com)
  • The cellular FLICE-inhibitory protein (c-FLIP) is a modulator of death receptor-mediated apoptosis and plays a major role in T- and B-cell homeostasis. (cdc.gov)
  • Overexpression of Short and Raji variants of Cellular FLICE-like inhibitory protein (c-FLIP) is capable of inhibiting apoptosis, while the function of the Long isoform depends of c-FLIPL concentration in cells. (bvsalud.org)
  • Cuando las variantes Short y Raji de la proteína Cellular FLICE-like inhibitory protein (c-FLIP) se encuentran sobrexpresadas son capaces de inhibir la apoptosis, mientras la función de la isoforma Long (c-FLIPL), depende de la concentración de esta molécula en las células. (bvsalud.org)
  • In our body, Carrier Proteins (Transport Proteins) are proteins that carry specific substances in the blood and across cell membranes. (wellnessadvocate.com)
  • In our body, the carrier proteins , Cholesterol Ester Transfer Proteins are a type of blood protein, that bind to and transfer cholesterol esters between lipoproteins, such as low-density lipoproteins and high-density lipoproteins. (wellnessadvocate.com)
  • In our body, as carrier proteins , GTP-Binding Proteins are regulatory proteins that act as molecular switches. (wellnessadvocate.com)
  • In our body, Iron-Binding Proteins are proteins that act as carrier proteins (transport proteins) for iron (Fe) . (wellnessadvocate.com)
  • Although CLL cells are commonly resistant to death receptor-induced apoptosis, VPA significantly increased sensitivity of leukemic cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and led to downregulation of c-FLIP (L) expression. (uliege.be)
  • As compared with treatment with Apo-2L/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or LAQ824 alone, pretreatment with LAQ824 increased the assembly of Fas-associated death domain and caspase-8, but not of c-FLIP, into the Apo-2L/TRAIL-induced death-inducing signaling complex. (unboundmedicine.com)
  • Tumor necrosis factor alpha (TNFα) is a proinflammatory cytokine involved in various biological processes including regulation of cell proliferation, differentiation, apoptosis and immune response. (wikipathways.org)
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (harvard.edu)
  • This graph shows the total number of publications written about "Tumor Necrosis Factor Receptor-Associated Peptides and Proteins" by people in Harvard Catalyst Profiles by year, and whether "Tumor Necrosis Factor Receptor-Associated Peptides and Proteins" was a major or minor topic of these publication. (harvard.edu)
  • Below are the most recent publications written about "Tumor Necrosis Factor Receptor-Associated Peptides and Proteins" by people in Profiles. (harvard.edu)
  • A 34 kDa signal transducing adaptor protein that associates with TUMOR NECROSIS FACTOR RECEPTOR TYPE 1. (sickkids.ca)
  • TRUSS, a novel tumor necrosis factor receptor 1 scaffolding protein that mediates activation of the transcription factor NF-kappaB. (ucdenver.edu)
  • Cell death can be divided into two types, apoptosis and necrosis [1] . (cusabio.com)
  • Here we show that Fadd(-/-) embryos contain raised levels of RIP1 and exhibit massive necrosis. (jefferson.edu)
  • Therefore, our data demonstrate an unexpected cell-type-specific interplay between FADD and RIP1, which is critical for the regulation of apoptosis and necrosis during embryogenesis and lymphocyte function. (jefferson.edu)
  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is currently under clinical development as a cancer therapeutic agent. (aacrjournals.org)
  • c-FLIP is expressed constitutively in many cell types, but its lifespan is short because its expression can be regulated by a variety of stimuli [1] . (cusabio.com)
  • For this purpose, the proteins associated with either CD95 or FADD were immunoprecipitated in freshly isolated GC B cells or in GC B cells cultured in complete medium without exogenous stimuli for different lengths of time. (nih.gov)
  • Boesen-de Cock, Tepper, de Vries, van Blitterswijk, Borst: Common regulation of apoptosis signaling induced by CD95 and the DNA-damaging stimuli etoposide and gamma-radiation downstream from caspase-8 activation. (antibodies-online.com)
  • Many apoptosis-inducing stimuli often induce autophagy, for instance, both apoptosis and autophagy are simultaneously upregulated by treatment in breast cancer cells with ceramide [3] . (cusabio.com)
  • The most intensively studied inflammasome comprises an oligomeric complex of procaspase-1 with the NLRP3 and ASC adapter proteins that rapidly assembles in response to diverse stress stimuli such as increased reactive oxygen species (ROS) ( 3 ), mitochondrial dysfunction ( 4 ), perturbation of intracellular ion homeostasis ( 5 - 7 ), disruption of lysosomal membrane integrity ( 8 ), and activation of deubiquitinases ( 9 - 11 ). (jimmunol.org)
  • This intracellular domain recruits a death-domain containing adaptor protein, TRADD by homophilic interactions. (wikipathways.org)
  • Apoptosis can be activated by a variety of cellular signals, including increased intracellular Ca 2+ concentration, reactive oxygen species (ROS) such as hydroxyl radicals caused by oxidative damage, toxins, NO, growth factors, and hormonal stimulation. (cusabio.com)
  • In addition, Akt activation was involved in CpG ODN-induced phosphorylation of FoxO3a, expression of FLIP, and anti-apoptosis. (bvsalud.org)
  • These proteins are typically activated through phosphorylation by the indicated upstream kinases. (pubmedcentralcanada.ca)
  • decreases CASP8 activity in a mitochondria localization- and phosphorylation-dependent manner and this interaction is dissociated by calcium (PubMed:15383280). (sdsc.edu)
  • Organic I is normally internalized and changed in the cytosol into complicated II by exchange of signaling proteins connected with TNFR1. (movd2016.org)
  • Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis . (wikipedia.org)
  • c-FLIP acts as a dominant-negative inhibitor to hinder apoptosis caused by death-inducing ligands through the binding of the FAS-associated death domain (FADD) protein and/or caspases-8 and caspase-10 at the level of the death-inducing signaling complex (DISC) [5] . (cusabio.com)
  • This results in cytochrome C release and activation of other caspases ultimately leading to apoptosis. (wikipathways.org)
  • Programmed cell death (apoptosis) is definitely a coordinated group of events eventually resulting in the substantial activation of specialised proteases (caspases) that cleave several substrates, orchestrating fairly standard biochemical shifts than culminate in mobile suicide. (movd2016.org)
  • Active caspase-8 initiates the subsequent cascade of caspases mediating apoptosis. (string-db.org)
  • Involved in the activation cascade of caspases responsible for apoptosis execution. (string-db.org)
  • The autoproteolytic processing of the caspases in the complex triggers a downstream caspase cascade, and leads to apoptosis. (avivasysbio.com)
  • PKCmu prevents CD95-mediated apoptosis and enhances proliferation in pancreatic tumour cells. (nih.gov)
  • We demonstrate that in these cells, PKCmu expression strongly correlates with resistance to CD95-induced apoptosis. (nih.gov)
  • In CD95-sensitive Colo357 cells, forced overexpression of PKCmu strongly reduced CD95-mediated apoptosis, an effect that could be reversed by pretreatment with Goe6983. (nih.gov)
  • The role of c-FLIP in modulation of CD95-induced apoptosis [J]. J. Biol. (cusabio.com)
  • Here, we show that GC B cell apoptosis is preceded by the rapid activation of caspase-8 at the level of CD95 death-inducing signaling complex (DISC). (nih.gov)
  • A) CD95 or (B) FADD was immunoprecipitated (IP) from 107 freshly isolated GC B cells or at different times after setting the same cells in culture in complete medium as described in Materials and Methods. (nih.gov)
  • The immunoprecipitates were washed, subjected to 10% SDS PAGE, and successively probed with the anti-caspase-8, FADD, CD95, and c-FLIP Abs. (nih.gov)
  • As a result, the abundant cFLIP L forms enzymatically active heterodimers with caspase 8 (CASP8) in MSMs, which prevents formation of proapoptotic CASP8 p10/p20 and cleaves receptor interacting protein kinase 1 (RIP1), thus setting up a higher threshold for CD95-mediated apoptosis and RIP1-mediated necroptosis. (pnas.org)
  • In B lymphocytes, induction of apoptosis or programmed cell death (PCD) by Fas (CD95/APO-1) is suppressed by the triggering of CD40. (ashpublications.org)
  • p>When browsing through different UniProt proteins, you can use the 'basket' to save them, so that you can back to find or analyse them later. (uniprot.org)
  • TNF receptor 1, receptor-interacting serine/threonine-protein 25332-39-2 supplier kinase 1, Fas-associated loss of life domain proteins, TNF receptor-associated loss of life domains (TRADD), TNF receptor-associated aspect, FLICE-like inhibitory proteins (a.k.a. (movd2016.org)
  • Protein kinases C (PKC) have been shown to be important in the regulation of proliferation and apoptosis. (nih.gov)
  • Activator protein 1 (AP1) 1 , 2 functions in almost all areas of eukaryotic cellular behaviour, from cell cycle proliferation and development to stress response and apoptosis. (pubmedcentralcanada.ca)
  • JUN is important for cell proliferation, survival and apoptosis, and accordingly mice lacking JUN die between day 12.5 and 13.5 of embryonal development owing to hepatic failure and heart defects 8 , 9 . (pubmedcentralcanada.ca)
  • The effects of knockdown of c-FLIPL on cell viability, proliferation and apoptosis were assessed by comparing with scrambled siRNA-transfected cells. (bvsalud.org)
  • Surprisingly, Fadd(-/-) mice die in utero and conditional deletion of FADD leads to impaired lymphocyte proliferation. (jefferson.edu)
  • Furthermore, RIP1 deficiency fully restored normal proliferation in Fadd(-/-) T cells but not in Fadd(-/-) B cells. (jefferson.edu)
  • It is now apparent that hypoxia, according to its severity, can either promote apoptosis and cell death or contrariwise prevent cell death by provoking an adaptive response leading to cell proliferation and tumor growth. (biomedcentral.com)
  • However, ectopic expression of Fas did not result in an induction of apoptosis in attached HUVECs, and neither did it sensitize the cells to CH11-mediated killing (see Fig. 6). (nih.gov)
  • Jun proteins can form stable dimers that bind to the AP1 DNA recognition element 5′-TGAC/GTCA-3′ (also known as TPA response element (TRE)) based on their ability to mediate transcriptional induction in response to the phorbol ester tumour promoter TPA 2 , 15 . (pubmedcentralcanada.ca)
  • Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. (string-db.org)
  • In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its ubiquitination and proteosomal degradation. (uniprot.org)
  • Exhibits kinase activity-dependent functions that trigger cell death and kinase-independent scaffold functions regulating inflammatory signaling and cell survival (PubMed:11101870, PubMed:25459879). (icr.ac.uk)
  • The death domain mediates dimerization and activation of its kinase activity during necroptosis and apoptosis (PubMed:29440439). (rcsb.org)
  • Functional complementation between FADD and RIP1 in embryos and lympho" by Haibing Zhang, Xiaohui Zhou et al. (jefferson.edu)
  • Functional complementation between FADD and RIP1 in embryos and lymphocytes. (jefferson.edu)
  • To investigate a potential in vivo functional interaction between RIP1 and FADD, null alleles of RIP1 were crossed into Fadd(-/-) mice. (jefferson.edu)
  • Notably, RIP1 deficiency allowed normal embryogenesis of Fadd(-/-) mice. (jefferson.edu)
  • Conversely, the developmental defect of Rip1(-/-) lymphocytes was partially corrected by FADD deletion. (jefferson.edu)
  • Fadd(-/-)Rip1(-/-) double-knockout T cells are resistant to death induced by Fas or TNF-α and show reduced NF-κB activity. (jefferson.edu)
  • Upon TNF-α binding, TNF receptor 1 (TNFR1) recruits receptor-interacting protein 1 (RIP1), cellular inhibitor of apoptosis protein 1 and 2 (cIAP1 and cIAP2), and TNFR-associated factor 2 (TRAF2) for the assembly of TNFR1-associated complex I ( 16 ). (aacrjournals.org)
  • TRAF2 and RIP1 then detach from TNFR1 and recruit FADD and caspase-8 for the assembly of the cytoplasmic complex II ( 19 ), where the deubiquitinating cylindromatosis removes the polyubiquitin chains from RIP1 to promote caspase-8 cleavage for TNF-α-induced apoptosis ( 20 ). (aacrjournals.org)
  • Conversely, short hairpin RNA-mediated knockdown of endogenous DARPP-32 sensitized the resistant MKN-45 cells to TRAIL-induced apoptosis and enhanced TRAIL-mediated activation of caspase-8, -9, and -3. (elsevier.com)
  • Although E8-expressing thymocytes were resistant to Fas-mediated apoptosis, the total number of thymocytes in 4-8-week-old E8 transgenic mice was more than 3-fold less than that in control littermates. (nih.gov)
  • Substantial numbers of colon cancer cells have been observed to express Fas/Fas ligand, but are resistant to Fas-mediated apoptosis, suggesting that colonic tumours might develop specific mechanisms to overcome Fas-mediated apoptosis. (elsevier.com)
  • TNF-R1 and TNF-R2 binds membrane-integrated TNF (memTNF) as well as soluble TNF (sTNF) TNF-R1 contains a protein-protein interaction domain, called death domain (DD). (wikipathways.org)
  • During embryonic development suppresses apoptosis and necroptosis and prevents the interaction of TRADD with FADD thereby limiting aberrant activation of CASP8 (By similarity). (icr.ac.uk)
  • The cytoplasmic domain of Fas has no enzymatic activity but contains a protein-interaction motif termed the "death domain. (pnas.org)
  • There is a complex interaction between autophagy and apoptosis . (cusabio.com)
  • A comprehensive and in-depth study of the interaction mechanism between autophagy and apoptosis will bring about breakthroughs in the cognition and treatment of diseases such as tumors. (cusabio.com)
  • There are three different types of interaction between autophagy and apoptosis. (cusabio.com)
  • this interaction is followed by CASP8 proteolytic cleavage and activation (By similarity). (sdsc.edu)
  • The interaction of this receptor with its ligand allows the formation of a death-inducing signaling complex that includes Fas-associated death domain protein (FADD), caspase 8, and caspase 10. (avivasysbio.com)
  • Kaiser, Upton, Mocarski: Receptor-interacting protein homotypic interaction motif-dependent control of NF-kappa B activation via the DNA-dependent activator of IFN regulatory factors. (antikoerper-online.de)
  • Although both splice variants regulate death receptor (DR)-induced apoptosis by CASP8, the specific role of each isoform is poorly understood. (pnas.org)
  • A single nucleotide polymorphism determines protein isoform production of the human c-FLIP protein. (cdc.gov)
  • Three different isoforms have been described on the protein level, including the long form c-FLIP(L) as well as 2 short forms, c-FLIP(S) and the recently identified c-FLIP(R). The mechanisms controlling c-FLIP isoform production are largely unknown. (cdc.gov)
  • The isoforms lacking the transmembrane domain may negatively regulate the apoptosis mediated by the full length isoform. (avivasysbio.com)
  • Plays a role in the regulation of the cytoskeleton by binding to gelsolin ( GSN ), sequestering the protein in an inactive conformation away from actin. (rcsb.org)
  • Requirement for Casper (c-FLIP) in regulation of death receptor-induced apoptosis and embryonic development. (cusabio.com)
  • Yet, regulation of apoptosis, an integral and crucial facet during the process of T-cell activation, is not well understood. (biomedcentral.com)
  • This inherently diverse composition of AP1 complexes and their central role in transcriptional regulation places AP1 complexes at a functional epicenter for pathological signal relay in disease, particularly in the context of malignant cellular transformation in which AP1 proteins are often deregulated by oncoprotein signalling 4 - 6 . (pubmedcentralcanada.ca)
  • Down regulation of c-FLIP L could increase the tumor apoptosis and enhance the antitumor response of T cells in the lymphocyte tumor cells co-culture system. (frontiersin.org)
  • Microbial infection) Interacts with human herpes simplex virus 1 (HHV-1) protein US11 in an RNA-dependent manner (PubMed:11836380). (rcsb.org)
  • Interacts with vaccinia protein E3 (PubMed:25740987). (rcsb.org)
  • Microbial infection) Interacts with vaccinia protein E3. (rcsb.org)
  • Interacts with CASP8 AP2 (PubMed:17245429). (sdsc.edu)
  • Interacts with FADD (PubMed:29440439). (sdsc.edu)
  • Microbial infection) Interacts with Murid herpesvirus 1 protein RIR1. (rcsb.org)
  • The resulting aggregate called death-inducing signaling complex (DISC) performs CASP8 proteolytic activation. (abcam.com)
  • The dimerization and cleavage of caspase-8 in the DISC are the critical upstream events in TNF family ligand-induced apoptosis ( 9 - 12 ), and ubiquitination of proteins in the DISC regulates these biochemical processes ( 13 ). (aacrjournals.org)
  • negatively regulate CASP8 through proteasomal degradation (By similarity). (sdsc.edu)
  • When cIAPs are absent, caspase activity is the "rheostat" that is controlled by cFLIP isoforms in the Ripoptosome and decides if cell death occurs by RIP3-dependent necroptosis or caspase-dependent apoptosis. (nih.gov)
  • A homolog of caspase 8 (CASP8), cFLIP exists in two main isoforms: cFLIP L (long) and cFLIP R (short). (pnas.org)
  • Zusätzlich bieten wir Ihnen RIPK3 Kits (27) und RIPK3 Proteine (16) und viele weitere Produktgruppen zu diesem Protein an. (antikoerper-online.de)
  • Embryonic lethality was completely prevented by the combined loss of Casp8 and Ripk3 , but not by loss of Ripk3 or Mlkl alone. (nature.com)
  • A low dose of kurarinone had no significant effect on apoptosis, but this compound markedly promoted tumor cell death through elevation of Bid cleavage, cytochrome c release and caspase activation in HeLa cells treated with TRAIL. (bvsalud.org)
  • Caspase inhibitors inhibited kurarinone-mediated cell death, which indicates that the cytotoxic effect of this compound is mediated by caspase-dependent apoptosis. (bvsalud.org)
  • Thus, matrix attachment protects cells from Fas-induced apoptosis, whereas matrix detachment results in susceptibility to Fas-mediated cell death. (nih.gov)
  • These studies identify matrix attachment as a survival factor against death receptor-mediated apoptosis and provide a molecular mechanism for anoikis and previously observed Fas resistance in endothelial cells. (nih.gov)
  • Apoptosis repressor that blocks multiple modes of cell death. (uniprot.org)
  • The N-terminal FADD -like death effector domain of this protein suggests that it may interact with Fas-interacting protein FADD. (wikipedia.org)
  • Taken together, these findings indicate that LAQ824 may have promising activity in augmenting Apo-2L/TRAIL-induced death-inducing signaling complex and apoptosis of human acute leukemia cells. (unboundmedicine.com)
  • Apoptosis induced by the death-inducing ligand FasL (CD95L) is a major mechanism of cell death. (semanticscholar.org)
  • Fas is a cell surface death receptor that regulates peripheral tolerance and lymphoid homeostasis. (pnas.org)
  • We have isolated a death domain mutant, termed FasΔ, that selectively binds Daxx but not FADD. (pnas.org)
  • An adapter protein, termed FADD or Mort1, binds to the Fas death domain and recruits pro-caspase-8, the zymogen form of an apical cell death protease ( 11 - 12 ). (pnas.org)
  • Several viral and cellular pro-caspase-8 like proteins, termed FLIPs ( 18 ), contain FADD-interacting DED motifs but inactive protease domains, and they are potent inhibitors of Fas-induced cell death in tissue culture cells and in primary lymphocytes ( 19 - 20 ). (pnas.org)
  • JNK has been previously implicated in activating apoptosis in vitro and in vivo ( 24 , 25 ), but its functional role in death-receptor signaling, as assayed by expressing dominant negative proteins, has been controversial ( 21 , 26 - 29 ). (pnas.org)
  • TNF Receptor-Associated Death Domain Protein" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (sickkids.ca)
  • It facilitates the recruitment of signaling proteins such as TNF RECEPTOR-ASSOCIATED FACTOR 2 and FAS ASSOCIATED DEATH DOMAIN PROTEIN to the receptor complex. (sickkids.ca)
  • Below are the most recent publications written about "TNF Receptor-Associated Death Domain Protein" by people in Profiles. (sickkids.ca)
  • The present study was undertaken to gain insights into the molecular mechanism of cell death (apoptosis) by guggulsterone, a constituent of Ayurvedic medicinal plant Commiphora mukul, using PC-3 human prostate cancer cells as a model. (isharonline.org)
  • Autophagy, also known as type II programmed cell death, a process in which denovo-formed membrane-enclosed vesicles engulf and consume cellular components, has been shown to engage in a complex interplay with apoptosis. (cusabio.com)
  • On another hand, it can lead to death itself, either in collaboration with apoptosis or as a back-up mechanism when the former is defective. (cusabio.com)
  • In this case, both autophagy and apoptosis are regulated to promote cell death. (cusabio.com)
  • In the death-inducing signaling complex, caspase-8 is cleaved and then initiates apoptosis through cleavage of downstream caspase-3 ( 15 ). (aacrjournals.org)
  • Mind bomb regulates cell death during TNF signaling by suppressing RIPK1's cytotoxic potential. (nature.com)
  • RCD - regulated cell death. (microbialcell.com)
  • In this short review, we discuss the differential implication of mitochondria in the major forms of regulated cell death. (microbialcell.com)
  • A20 is highly expressed in glioblastomas and, together with the death receptor 5 and receptor-interacting protein 1, forms a plasma membrane-bound preligand assembly complex under physiologic conditions. (aacrjournals.org)
  • In the death-inducing signaling complex, the C-terminal zinc finger (Znf) domain of the A20 ubiquitin ligase mediates receptor-interacting protein 1 polyubiquitination through lysine-63-linked polyubiquitin chains, which bind to the caspase-8 protease domain and inhibit caspase-8 dimerization, cleavage, and the initiation of TRAIL-induced apoptosis in glioblastoma-derived cell lines and tumor-initiating cells. (aacrjournals.org)
  • Taken together, these results demonstrate the involvement of Akt-FoxO3a in TLR9-mediated anti-apoptosis and indicate that FoxO3a is a distinct regulator for FLIP expression. (bvsalud.org)
  • We demonstrate here that matrix attachment is an efficient regulator of Fas-mediated apoptosis in endothelial cells. (nih.gov)
  • In our diet and our body, Calcium-Binding Proteins , the proteins to which calcium ions are bound, may act as transport proteins, as regulator proteins, and as activator proteins. (wellnessadvocate.com)
  • Since c-FLIP is a major regulator of DR-induced apoptosis, and since the aberrant c-FLIP expression is intertwined with a rising number of pathologies, detecting c-FLIP levels might be valuable to diagnosis, and drugs that only change c-FLIP-expression levels will certainly be a benefit in the treatment of relevant diseases [7] . (cusabio.com)
  • Can regulate NLRP3 inflammasome assembly and the activation of NLRP3 , NLRP1 , AIM2 and NLRC4 inflammasomes. (rcsb.org)
  • Can trigger apoptosis via FADD -mediated activation of CASP8 . (rcsb.org)
  • CDDP down-regulated c-FLIP, tending to lower the activation threshold required for TRAIL-induced caspase-8 activation. (unboundmedicine.com)
  • The CDDP-pretreated cells indeed demonstrated more increased TRAIL-mediated caspase-8 activation, loss of mitochondrial membrane potential (DeltaPsi(m)), and apoptosis than untreated cells. (unboundmedicine.com)
  • There is evidence of an early attempt to signal for apoptosis, which precedes the activation of NF-κB. (wikipathways.org)
  • The process of proper T-cell activation is strictly monitored and regulated by apoptosis signaling. (biomedcentral.com)
  • Furthermore, it provided a comprehensive temporal analysis of the transcriptional program of apoptosis associated with T-cell activation. (biomedcentral.com)
  • It engages other DD-containing proteins as well as a central (intermediate) region important for NF-kB activation and RHIM-dependent signaling (PubMed:10356400). (rcsb.org)
  • Notably, Dox-induced production of mature IL-1β was temporally correlated with caspase-8 activation in WT cells and greatly suppressed in Casp8 −/− Rip3 −/− or Trif −/− BMDC, as well as in WT BMDC treated with the caspase-8 inhibitor, IETD. (jimmunol.org)
  • abstract = "Purpose: Dopamine and cAMP-regulated phosphoprotein, Mr 32,000 (DARPP-32), is overexpressed during the gastric carcinogenesis cascade. (elsevier.com)
  • In our body, GTP-Binding Proteins activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP (the GTP phosphohydrolases ). (wellnessadvocate.com)
  • In our body, Insulin-Like Growth Factor Binding Protein is a family of soluble proteins that bind insulin-like growth factors and modulate their biological actions at the cellular level. (wellnessadvocate.com)
  • In protein science , Iron-Binding Proteins are metalloproteins that specifically bind to iron (Fe) . (wellnessadvocate.com)
  • It is through these domains that AP1 proteins dimerize and bind to DNA. (pubmedcentralcanada.ca)