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 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.
Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.
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.
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.
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 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.
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.
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.
Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.
Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.
A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 12 is activated by pro-apoptotic factors that are released during cell stress and by CARD SIGNALING ADAPTOR PROTEINS. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.
A short pro-domain caspase that is almost exclusively expressed in the EPIDERMIS and may play a role in the differentiation of epidermal KERATINOCYTES.
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.
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.
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.
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.
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)
A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
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)
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.
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.
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 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.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
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 CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
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.
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.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.
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.
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 cell line derived from cultured tumor cells.
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.
Peptides composed of between two and twelve amino acids.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Established cell cultures that have the potential to propagate indefinitely.
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.
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.
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.
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.
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.
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.
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 protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.
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.
Transport proteins that carry specific substances in the blood or across cell membranes.
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 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.
Physiologically inactive substances that can be converted to active enzymes.
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.
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.
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.
Multimeric protein complexes formed in the CYTOSOL that play a role in the activation of APOPTOSIS. They can occur when MITOCHONDRIA become damaged due to cell stress and release CYTOCHROME C. Cytosolic cytochrome C associates with APOPTOTIC PROTEASE-ACTIVATING FACTOR 1 to form the apoptosomal protein complex. The apoptosome signals apoptosis by binding to and activating specific INITIATOR CASPASES such as CASPASE 9.
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.
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.
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.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
A death domain receptor signaling adaptor protein that plays a role in signaling the activation of INITIATOR CASPASES such as CASPASE 2. It contains a death domain that is specific for RIP SERINE-THEONINE KINASES and a caspase-binding domain that binds to and activates CASPASES such as CASPASE 2.
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.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
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.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
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.
A family of intracellular signaling adaptor proteins that contain caspase activation and recruitment domains. Proteins that contain this domain play a role in APOPTOSIS-related signal transduction by associating with other CARD domain-containing members and in activating INITIATOR CASPASES that contain CARD domains within their N-terminal pro-domain region.
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.
Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including NEUROPEPTIDES; CYTOSKELETAL PROTEINS; proteins from SMOOTH MUSCLE; CARDIAC MUSCLE; liver; platelets; and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. This enzyme was formerly listed as EC
A family of serine endopeptidases found in the SECRETORY GRANULES of LEUKOCYTES such as CYTOTOXIC T-LYMPHOCYTES and NATURAL KILLER CELLS. When secreted into the intercellular space granzymes act to eliminate transformed and virus-infected host cells.
Elements of limited time intervals, contributing to particular results or situations.
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.
Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.
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.
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.
Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.
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 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.
Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.
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.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Glycoproteins found on the membrane or surface of cells.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
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.
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.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
A family of 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.
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
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.
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.
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.
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
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).
Proteins prepared by recombinant DNA technology.
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.
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.
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.
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 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.
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.
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.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
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.
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.
A RIP serine-theonine kinase that contains a C-terminal caspase activation and recruitment domain. It can signal by associating with other CARD-signaling adaptor proteins and INITIATOR CASPASES that contain CARD domains within their N-terminal pro-domain region.
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 action of a drug in promoting or enhancing the effectiveness of another drug.
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.
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.
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.
Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).
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)
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.
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 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.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.
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.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
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).
Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.
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.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
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).
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.
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.
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.
Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.
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.
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.
Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).
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.
Compounds that inhibit cell production of DNA or RNA.
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.
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.
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.
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.
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
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.
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.
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.
A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.
Proteins found in any species of virus.
The process of cleaving a chemical compound by the addition of a molecule of water.
A fractionated cell extract that maintains a biological function. A subcellular fraction isolated by ultracentrifugation or other separation techniques must first be isolated so that a process can be studied free from all of the complex side reactions that occur in a cell. The cell-free system is therefore widely used in cell biology. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p166)
That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
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.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
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.
Preparations of cell constituents or subcellular materials, isolates, or substances.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Various physiological or molecular disturbances that impair ENDOPLASMIC RETICULUM function. It triggers many responses, including UNFOLDED PROTEIN RESPONSE, which may lead to APOPTOSIS; and AUTOPHAGY.
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.
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.
A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.
Adenine nucleotides which contain deoxyribose as the sugar moiety.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.
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.
Nuclear matrix proteins that are structural components of the NUCLEAR LAMINA. They are found in most multicellular organisms.
A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
Proteins found in any species of insect.
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.
The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)
The 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.
Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.
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.
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.
An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.
A lysosomal cysteine proteinase with a specificity similar to that of PAPAIN. The enzyme is present in a variety of tissues and is important in many physiological and pathological processes. In pathology, cathepsin B has been found to be involved in DEMYELINATION; EMPHYSEMA; RHEUMATOID ARTHRITIS, and NEOPLASM INVASIVENESS.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
An antibiotic produced by Pseudomonas cocovenenans. It is an inhibitor of MITOCHONDRIAL ADP, ATP TRANSLOCASES. Specifically, it blocks adenine nucleotide efflux from mitochondria by enhancing membrane binding.
The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.
The process by which chemical compounds provide protection to cells against harmful agents.
One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.
A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of LACTATE and PYRUVATE. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist.
A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
A subclass of ubiquitously-expressed lamins having an acidic isoelectric point. They are found to remain bound to nuclear membranes during mitosis.
An indole-dione that is obtained by oxidation of indigo blue. It is a MONOAMINE OXIDASE INHIBITOR and high levels have been found in urine of PARKINSONISM patients.
A type I keratin found associated with KERATIN-8 in simple, or predominately single layered, internal epithelia.
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)
A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.
A group of acylated oligopeptides produced by Actinomycetes that function as protease inhibitors. They have been known to inhibit to varying degrees trypsin, plasmin, KALLIKREINS, papain and the cathepsins.
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.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
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.
A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.
A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)
Agents that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags.

Molecular cloning and characterization of two novel pro-apoptotic isoforms of caspase-10. (1/114)

Caspase-10/a (Mch4) and caspase-10/b (FLICE2) are related death effector domain-containing cysteine aspartases presumed to be at or near the apex of apoptotic signaling pathways. We report the cloning and characterization of two novel proteins that are splice isoforms of the caspase-10 family. Caspase-10/c is a truncated protein that is essentially a prodomain-only form of the caspase that lacks proteolytic activity in vitro but efficiently induces the formation of perinuclear filamentous structures and cell death in vivo. Caspase-10/c mRNA is specifically up-regulated upon TNF stimulation, suggesting a potential role of this isoform in amplifying the apoptotic response to extracellular stimuli such as cytokines. Caspase-10/d is a hybrid of the known caspases Mch4 and FLICE2, as it is identical to FLICE2 except for the small (p12) catalytic subunit, which is identical to Mch4. Caspase-10/d is proteolytically active in vitro and also induces cell death in vivo, although it is less active than Mch4. The mRNAs for all known isoforms of caspase-10 are abundantly expressed in fetal lung, kidney, and skeletal muscle but are very poorly expressed or absent in these tissues in the adult, implying a possible role for the caspase-10 family in fetal development.  (+info)

Impairment of TNF-receptor-1 signaling but not fas signaling diminishes T-cell apoptosis in myelin oligodendrocyte glycoprotein peptide-induced chronic demyelinating autoimmune encephalomyelitis in mice. (2/114)

T-cell apoptosis in inflammatory demyelinating lesions of chronic myelin oligodendrocyte glycoprotein peptide35-55 induced autoimmune encephalomyelitis was studied in several different gene knockout mice as well as their wild-type counterparts. The gene deletions included tumor necrosis factor (TNF) alpha, lymphotoxin, TNF receptor 1 or 2, Fas-L, inducible nitric oxide synthase, perforin, and interleukin1beta-converting enzyme. Impairment of the TNF receptor 1 pathway led to a 50% reduction of T-cell apoptosis in the central nervous system lesions, whereas the other genetic deletions showed no significant effect. Our study thus identified the TNF receptor 1 signaling pathway as one mechanism responsible for the removal of T lymphocytes from inflammatory demyelinating lesions of the central nervous system.  (+info)

Caspases in T-cell receptor-induced thymocyte apoptosis. (3/114)

Apoptosis eliminates inappropriate or autoreactive T lymphocytes during thymic development. Intracellular mediators involved in T-cell receptor (TCR)-mediated apoptosis in developing thymocytes during negative selection are therefore of great interest. Caspases, cysteine proteases that mediate mature T-cell apoptosis, have been implicated in thymocyte cell death, but their regulation is not understood. We examined caspase activities in distinct thymocyte subpopulations that represent different stages of T-cell development. We found caspase activity in CD4+CD8+ double positive (DP) thymocytes, where selection involving apoptosis occurs. Earlier and later thymocyte stages exhibited no caspase activity. Only certain caspases, such as caspase-3 and caspase-8-like proteases, but not caspase-1, are active in DP thymocytes in vivo and can be activated when DP thymocytes are induced to undergo apoptosis in vitro by TCR-crosslinking. Thus, specific caspases appear to be developmentally regulated in thymocytes.  (+info)

Inherited human Caspase 10 mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome type II. (4/114)

Caspases are cysteine proteases that mediate programmed cell death in phylogenetically diverse multicellular organisms. We report here two kindreds with autoimmune lymphoproliferative syndrome (ALPS) type II, characterized by abnormal lymphocyte and dendritic cell homeostasis and immune regulatory defects, that harbor independent missense mutations in Caspase 10. These encode amino acid substitutions that decrease caspase activity and interfere with death receptor-induced apoptosis, particularly that stimulated by Fas ligand and TRAIL. These results provide evidence that inherited nonlethal caspase abnormalities cause pleiotropic apoptosis defects underlying autoimmunity in ALPS type II.  (+info)

Structure, expression, and function of the Xenopus laevis caspase family. (5/114)

Caspases, a family of cysteine proteases, have been recognized as the central executors of programmed cell death. Nonetheless, the information on the caspase family has been limited to mammals, Drosophila, and nematodes. To examine the structure and characterization of the Xenopus caspase family, we have cloned the cDNAs encoding caspase-2 and -6-10 in addition to caspase-1 and -3, which we characterized previously (Yaoita, Y., and Nakajima, K. (1997) J. Biol. Chem. 272, 5122-5127). First, the existence of these caspases in frog suggests that the caspase cascades clarified in mammals are conserved at least from Amphibia. Interestingly, Xenopus caspase-1, -8, and -10 (especially caspase-8) showed a lower degree of identity to human equivalents than the other caspases. Second, mRNAs of many caspases increased during the climax of metamorphosis in regressing organs, tail, and intestine, where programmed cell death occurs, but not in apoptotic tail-derived cultured cells (XLT-15-11) treated with thyroid hormone, showing that new RNA synthesis of caspases is dispensable to programmed cell death. Third, comparison of human and Xenopus caspase sequences implies that some proposed regulations of human caspases are not conserved in frog.  (+info)

Activation of the NF-kappaB pathway by caspase 8 and its homologs. (6/114)

Caspase 8 is the most proximal caspase in the caspase cascade and has been known for its role in the mediation of cell death by various death receptors belonging to the TNFR family. We have discovered that Caspase 8 can activate the NF-kappaB pathway independent of its activity as a pro-apoptotic protease. This property is localized to its N-terminal prodomain, which contains two homologous death effector domains (DEDs). Caspase 10 and MRIT, two DEDs-containing homologs of Caspase 8, can similarly activate the NF-kappaB pathway. Dominant-negative mutants of the Caspase 8 prodomain can block NF-kappaB induced by Caspase 8, FADD and several death receptors belonging to the TNFR family. Caspase 8 can interact with multiple proteins known to be involved in the activation of the NF-kappaB pathway, including the serine-threonine kinases RIP, NIK, IKK1 and IKK2. Thus, DEDs-containing caspases and caspase homolog(s) may have functions beyond their known role in the mediation of cell death. Oncogene (2000) 19, 4451 - 4460.  (+info)

Resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in neuroblastoma cells correlates with a loss of caspase-8 expression. (7/114)

Disruption of apoptotic pathways may be involved in tumor formation, regression, and treatment resistance of neuroblastoma (NB). Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent inducer of apoptosis in cancer cell lines, whereas normal cells are not sensitive to TRAIL-mediated apoptosis. In this study we analyzed the expression and function of TRAIL and its agonistic and antagonistic receptors as well as expression of cellular FLICE-like inhibitory protein and caspase-2, -3, -8, -9, and -10 in 18 NB cell lines. Semiquantitative RT-PCR revealed that TRAIL-R2 and TRAIL-R3 are the main TRAIL-receptors used by NB cells. Sensitivity to TRAIL-induced apoptosis did not correlate with mRNA expression of TRAIL receptors or cellular FLICE-like inhibitory protein. Surprisingly, caspase-8 and caspase-10 mRNA expression was detected in only 5 of 18 NB cell lines. Interestingly, only these five NB cell lines were susceptible to TRAIL-induced apoptosis in a time- and dose-dependent manner. Treatment with 5-aza-2'-deoxycytidine restored mRNA and protein expression of caspase-8 and TRAIL sensitivity of resistant cell lines, suggesting that gene methylation is involved in caspase inactivation. The TRAIL system seems to be functional in NB cells expressing caspase-8 and/or caspase-10. Because many cytotoxic drugs induce caspase-dependent apoptosis, failure to express caspase-8 and/or caspase-10 might be an important mechanism of resistance to chemotherapy in NB.  (+info)

Progressive resistance to apoptosis in a cell lineage model of human proliferative breast disease. (8/114)

BACKGROUND: Proliferative breast disease (PBD) may increase a woman's risk of developing breast cancer, perhaps by decreasing cellular sensitivity to apoptosis. To determine whether resistance to apoptosis develops during PBD, we investigated apoptosis initiated through the Fas pathway in a series of cell lines that recapitulates the morphologic changes of PBD in nude/beige mice. METHODS: The series of cell lines used was MCF-10A cells (parental preneoplastic human breast epithelial cells), MCF-10AT cells (transformed with T(24) Ha-ras), and MCF-10ATG3B cells (derivative cells that progress to carcinoma). Fas-mediated apoptosis, induced when a Fas monoclonal antibody bound to and activated the Fas receptor on these cells, was assessed morphologically and by flow cytometry. Levels of proteins involved in Fas-mediated apoptosis and cleavage of poly(adenosine diphosphate-ribose) polymerase (PARP), an end product of caspase activation, were determined by immunoblotting. Bcl-2 and Bax heterodimerization was examined by coimmunoprecipitation. All statistical tests were two-sided. RESULTS: Sensitivity to Fas-mediated apoptosis decreased with the tumorigenic potential of cells: MCF-10A cells were extremely susceptible, MCF-10AT cells were less susceptible, and MCF-10ATG3B cells were resistant. The percentage of apoptotic cells declined, from 24% to 8% to 6%, respectively. All lines produced Fas ligand (FasL) and had comparable levels of Fas receptor, FasL, Fas-associated death-domain protein, and caspases 3 and 6. Levels of caspase 8 were similar in MCF-10A and MCF-10AT cells but about 30% lower in MCF-10ATG3B cells (P>.01 but <.05). Levels of caspase 10 were about 20% lower in MCF-10AT cells (P>.005 but <.01) and about 59% lower in MCF-10ATG3B cells than in MCF-10A cells (P>.01 but <.05). PARP cleavage was detected in MCF-10A and MCF-10AT cells but not in MCF-10ATG3B cells. Levels of Bax, Bid, and Bak proteins were similar in all lines, but levels of Bcl-2 were lower in MCF-10AT and MCF-10ATG3B cells than in MCF-A cells, and Bcl-2-Bax heterodimerization progressively declined in the series. CONCLUSION: Resistance to Fas-mediated apoptosis appears to develop progressively in the MCF-10AT cell series.  (+info)

Classzone Use this site to review the basics of this unit. Choose high school science, Kentucky and the green biology book for Kentucky. Although this site does not review all of the required information it does cover much of the basic information. ...
Bax is a Bcl-2 protein crucial for apoptosis initiation and execution, whose active conformation is only partially understood. Dipolar EPR spectroscopy has proven to be a valuable tool to determine coarse-grained models of membrane-embedded Bcl-2 proteins. Here we show how the combination of spectroscopically distinguishable nitroxide and gadolinium spin labels and Double Electron-Electron Resonance can help to gain new insights into the quaternary structure of active, membrane-embedded Bax oligomers. We show that attaching labels bulkier than the conventional MTSL may affect Bax fold and activity, depending on the protein/label combination. However, we identified a suitable pair of spectroscopically distinguishable labels, which allows to study complex distance networks in the oligomers that could not be disentangled before. Additionally, we compared the stability of the different spin-labeled protein variants in E. coli and HeLa cell extracts. We found that the gem-diethyl nitroxide-labeled Bax
Mouse anti Human caspase-14, clone 4C9 recognizes human caspase-14, a 242 amino acid ~28 kDa non-apoptotic caspase which exists as a
Complete information for CASP5 gene (Protein Coding), Caspase 5, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
1196 (10 years ago) by hstehr: new class for scoring all casp7/casp8/casp9 server models in terms of GDT_TS and Acc/Cov of the contact map ...
The quake in northeastern Italy destroyed more than 300 000 wheels of Parmesan and Grana Padano, a similar cheese, with an estimated value of more than €250m.
BioAssay record AID 513048 submitted by ChEMBL: Inhibition of human caspase-3-mediated apoptosis assessed as Ac-DEVD-7-amino-4-methylcoumarin cleavage product at 100 uM by fluorescence assay.
CASP1 - CASP1 (untagged)-Human caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) (CASP1), transcript variant gamma available for purchase from OriGene - Your Gene Company.
CASP5 - CASP5 (untagged)-Human caspase 5, apoptosis-related cysteine peptidase (CASP5), transcript variant d available for purchase from OriGene - Your Gene Company.
Autoimmune lymphoproliferative syndrome (ALPS) is characterized by nonmalignant lymphadenopathy, splenomegaly, and autoimmune cytopenias. In 1995, defective lymphocyte apoptosis secondary to mutations in the FAS gene was identified as a molecular basis for ALPS.
The purpose of the protocol is to allow for patients, and relatives of patients, who may have the newly described autoimmune lymphoproliferative syndrome, to be evaluated at the NIH Clinical Center. This evaluation will include blood and relevant tissue studies along with long-term clinical evaluations to define the biology, inheritance,clinical spectrum, and natural history of this syndrome. The aim of the research is to understand mechanisms involved in the development of expanded numbers of what is typically a rare population of immune cells (CD4-8-/TCRalpha/beta+ T cells, otherwise referred to as double negative T cells), and how these relate to the development of expanded numbers of immune cells and autoimmune (self against self) responses in patients with ALPS.. In some cases, we may proivide treatment related to ALPS. These treatments are consistent with standard medical practice.. Participants with ALPS will be invited to visit the NIH once a year or more frequently when clinically ...
Langan RC, Gill F, Raiji MT, Mullinax JE, Pittaluga S, Pandalai P, Davis J, Perkins K, Avital I, Rudloff U. Autoimmune pancreatitis in the autoimmune lymphoproliferative syndrome (ALPS): a sheep in wolves clothing? Pancreas. 2013 Mar; 42(2):363-6 ...
AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; ALPS description, symptoms and related genes. Get the complete information in our medical search engine for p
The nomenclature for the various types of ALPS is determined based on the genetic mutation present in an individual. Patients meeting diagnostic criteria for ALPS in whom no genetic mutation can be id... more
Although specific mutations that cause ALPS have been identified, no environmental exposures or risk factors have yet been associated with an increased prevalence of the disease. Certainly, any patien... more
A fundamental biological question that remains largely unresolved concerns the mechanism by which binding of ligands to receptors on the cell surface causes transmission of a signal through the plasma membrane. One appealing explanation has been that ligand binding brings receptors together into multimeric complexes. Three reports describe cases in which the opposite approach is taken, and the receptors are bound and lie in wait for the ligand. Siegel et al. and Chan et al. have examined how the Fas and tumor necrosis factor (TNF) receptors signal. They define a protein interaction domain in these receptors that mediates assembly of the receptors into complexes in the absence of ligand. Such association is shown to be necessary for ligand binding and subsequent signaling. The results also explain how abnormal forms of Fas can dominantly prevent Fas-induced signaling in the human disease known as autoimmune lymphoproliferative syndrome. When bound to their cognate receptors, interferons (IFNs) ...
Personal/non-self discrimination characterizes immunity and allows responses against pathogens but not self-antigens. non-described p21 function in limiting T cell overactivation and overproduction of IFN-γ a key lupus cytokine. p21 did Rasagiline not affect normal T cell responses revealing differential p21 requirements for autoreactive and normal T cell activity regulation. The underlying concept of these findings suggests potential treatments for lupus and autoimmune lymphoproliferative syndrome without compromising normal immunity. p21 (WAF1) is known mainly for its cell cycle inhibitor properties; it regulates early G1-S changeover by inhibiting cyclin-dependent kinases in organic with cyclins A and D1 or E. It was primarily assumed that p21 deletion would result in extensive tumor advancement but p21-lacking mice are essentially cancer-free2 3 Insufficiency in p21 coupled with minor autoreactive backgrounds such as for example 129/Sv × C57BL/64 or the Gadd45a-lacking mice show serious ...
Free Online Library: Programmed Death Ligand-1 (PD-L1) Expression in the Programmed Death Receptor-1 (PD-1)/PD-L1 Blockade: A Key Player Against Various Cancers.(Report) by Archives of Pathology & Laboratory Medicine; Health, general Apoptosis Research Gene expression
Summary of CASP8 (Casp-8, FLICE, MACH, MCH5) expression in human tissue. Cytoplasmic expression of varying intensity in most tissues.
Treatment is most commonly directed at autoimmune disease and may be needed to treat bulky lymphoproliferation. First line therapies include corticosteroids (very active but toxic with chronic use), and IVIgG, which are not as effective as in other immune cytopenia syndromes. Second line therapies include: mycophenolate mofetil (cellcept)[15] which inactivates inosine monophosphate, most studied in clinical trials with responses varying (relapse, resolution, partial response). It does not affect lymphoproliferation or reduce DNTs, with no drug-drug interactions. This treatment is commonly used agent in patients who require chronic treatment based on tolerance and efficacy. It may cause hypogammaglobulinemia (transient) requiring IVIgG replacement. Sirolimus (rapamycin, rapamune) which is a mTOR (mammalian target of rapamycin) inhibitor[16] can be active in most patients and can in some cases lead to complete or near-complete resolution of autoimmune disease (,90%)[17][18] With this treatment ...
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Covered on Genetics Home Reference: autoimmune lymphoproliferative syndromebreast cancerFrom NCBI Gene: Caspase-8 deficiencyHepatocellular carcinomaFamilial cancer of breastLung cancerFrom UniProt: Caspase-8 deficiency (CASP8D): Disorder resembling autoimmune lymphoproliferative syndrome (ALPS). It is characterized by lymphadenopathy, splenomegaly, and defective CD95-induced apoptosis of peripheral blood lymphocytes (PBLs). It leads to defects in activation of T-lymphocytes, B-lymphocytes, and natural killer cells leading to immunodeficiency characterized by recurrent sinopulmonary and herpes simplex virus infections and poor responses to immunization. [MIM:607271] From NCBI Gene: This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes composed of a prodomain, a large protease subunit, and a small protease subunit. Activation of ...
Caspase-10 is an enzyme that, in humans, is encoded by the CASP10 gene. This gene encodes a protein that is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein cleaves and activates caspases 3 and 7, and the protein itself is processed by caspase 8. Mutations in this gene are associated with apoptosis defects seen in type II autoimmune lymphoproliferative syndrome. Three alternatively spliced transcript variants encoding different isoforms have been described for this gene. Caspase 10 has been shown to interact with FADD, CFLAR, Caspase 8, Fas receptor, RYBP, TNFRSF1A and TNFRSF10B. The Proteolysis Map Caspase GRCh38: Ensembl release 89: ENSG00000003400 - Ensembl, May 2017 Human PubMed ...
This study will evaluate the safety and effectiveness of an antibiotic called Fansidar on autoimmune lymphoproliferative syndrome (ALPS). Patients with ALPS have enlarged lymph glands, spleen and/or liver, abnormal blood cell counts and overactive immune function. Current treatments are aimed at suppressing the immune system and improving symptoms, such as anemia (low red blood cell count) and low white blood cell and platelet counts. These treatments, however, are only partially effective and may have complications. Fansidar is a combination of two drugs, sulfadoxine and pyrimethamine, that is used to treat or prevent parasitic infections such as malaria. Recently a child with ALPS who was treated with Fansidar for a different illness had a marked shrinkage of the lymph organs. This study will examine whether Fansidar can shrink the lymph glands or spleen in patients with ALPS.. Patients with ALPS between the ages of 4 and 70 years who have had lymph gland enlargement for at least 1 year and ...
Teachey DT, Manno CS, Axsom KM, et al: Unmasking Evans syndrome: T-cell phenotype and apoptotic response reveal autoimmune lymphoproliferative syndrome (ALPS). Blood 2005;105:2443-2448. Bader-Meunier B, Rieux-Laucat F, Croisille L, et al: Dyserythropoiesis associated with a fasdeficient condition in childhood. Br J Haematol 2000;108:300-304. Pensati L, Costanzo A, Ianni A, et al: Fas/Apo1 mutations and autoimmune lymphoproliferative syndrome in a patient with type 2 autoimmune hepatitis. Gastroenterology 1997;113: 1384-1389. Cell 1997;89:1067-1076. Stanger B, Leder P, Lee T, Kim E, Seed B: RIP: A novel protein containing a death domain that interacts with fas/APO-1(CD95) in yeast and causes cell death. Cell 1995;81:513-523. Chu K, Niu X, Williams LT: A Fas-associated protein factor, FAF1, potentiates Fas-mediated apoptosis. Proc Natl Acad Sci USA 1995;92:11894-11898. Barnhart BC, Alappat EC, Peter ME: The CD95 type I/type II model. Semin Immunol 2003;15: 185-193. Siegel RM, Muppidi JR, Sarker M, ...
Caspases are cysteine proteases that mediate programmed cell death in phylogenetically diverse multicellular organisms. We report here two kindreds with autoimmune lymphoproliferative syndrome (ALPS) type II, characterized by abnormal lymphocyte and dendritic cell homeostasis and immune regulatory d …
Human caspase 2 ELISA kit can be used for detecting in vitro quantitative levels of caspase-2 (CASP2) in human serum, cell culture supernatant, plasma, tissue
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Variants in CASP10 cause autoimmune lymphoproliferative syndrome through a likely dominant negative mechanism. A single report of an exonic deletion leading to a frameshift was reported in one patient with systemic juvenile idiopathic arthritis (Tadaki H et al.). The deletion was inherited from a normal parent. Of note, SNPs polymorphism of CASP10 were found to be associated with risk of gastric cancers, cardia adenocarcinomas, and gastric noncardia adenocarcinomas (PMID 23921907). SNPs loci of CASP10 were also identified associated with susceptibility of chronic lymphocytic leukemia or small lymphocytic lymphoma (PMID 23770605), breast cancer (PMID 23212337), and cutaneous melanoma (PMID 18563783).. ...
Expression of CASP8 (Casp-8, FLICE, MACH, MCH5) in soft tissue 2 tissue. Antibody staining with HPA001302, HPA005688 and CAB002047 in immunohistochemistry.
zVAD-fmk does not totally abrogate FasL-triggered apoptosis in HeLa cells expressing caspase-10 at low level.A, B, Casp10+ and Casp10- HeLa cells were incubated
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This synthetic peptide sequence is selected from human CASP3 construct and is used as the immunogen for PAB2069. (P2577) - Products - Abnova
09:39, 30 April 2015 Homo sapiens:Apoptosis Modulation and Signaling‎ (Corrected ID for AIFM1,CASP4,CASP2,CASP1,HSPA1A,PIDD,TP53,PRKD1,NAIP,XIAP,AIFM2,RIPK1 and PEA15 genes) ...
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Although ALPS is frequently caused by mutations in known genes, such as FAS, FASLG or CASP10, in 20-30% of cases the defect is still unknown. It is highly likely that defects in or overexpression of regulators of these genes such as miR-146a22 could result in an ALPS-like phenotype and account for a not yet defined percentage of ALPS-U cases. In the present study we identified an IL12RB1 mutation and the IL12 signaling pathway as such an alternative cause of an ALPS-like phenotype through regulation of FasL expression. Previously it was shown that activation of T and NK cells by IL12 results in upregulation of FasL.23-26,28,42 For instance, Yu et al. showed that dendritic cell-derived IL12 is involved in upregulation of FasL on NK cells leading to cell death.25 Moreover, in the absence of antigen, IL12 induces apoptosis of T cells via upregulation of FasL which can be blocked by anti-FasL antibodies.26 In line with this, we found that primary human T cells deficient in FasL expression were ...
Complete information for CASP8AP2 gene (Protein Coding), Caspase 8 Associated Protein 2, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Antho 50 induces caspase 3 activation and UHRF1 down-regulation independently of p53 and p73.B CLL cells were incubated with Antho 50 at 75 μg/mL for the ind
Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... This protein cleaves and activates caspases 3 and 7, and the protein itself is processed by caspase 8. Mutations in this gene ... Caspase 8, Fas receptor, RYBP, TNFRSF1A and TNFRSF10B. The Proteolysis Map Caspase GRCh38: Ensembl release 89: ENSG00000003400 ... Caspase-10 is an enzyme that, in humans, is encoded by the CASP10 gene. This gene encodes a protein that is a member of the ...
... as are caspase-2 (EC, caspase-8 (EC and caspase-9 (EC Chang HY, Yang X (December 2000). " ... Shikama Y, Yamada M, Miyashita T (July 2003). "Caspase-8 and caspase-10 activate NF-kappaB through RIP, NIK and IKKalpha ... Fischer U, Stroh C, Schulze-Osthoff K (January 2006). "Unique and overlapping substrate specificities of caspase-8 and caspase- ... Caspase-10 (EC, FLICE2, Mch4, CASP-10, ICE-like apoptotic protease 4, apoptotic protease Mch-4, FAS-associated death ...
... -1, Caspase-4, Caspase-5 and Caspase-11 are considered 'Inflammatory Caspases'. Caspase-1 is key in activating pro- ... Apoptopic caspases are subcategorised as: Initiator Caspases (Caspase 2, Caspase 8, Caspase 9, Caspase 10) Executioner Caspases ... Caspase-1, Caspase-4 and Caspase-5 in humans, and Caspase-1 and Caspase-11 in mice play important roles in inducing cell death ... Pyroptosis by Caspase-4 and Caspase-5 in humans and Caspase-11 in mice These caspases have the ability to induce direct ...
Caspase-2, Caspase-3, Caspase-6, Caspase-7, Caspase-9, DEDD, FADD, FasL, FasR, IFT57, NOL3, PEA15, RIPK1, TNFRSF10B, and TRAF1 ... Caspase-8 is a caspase protein, encoded by the CASP8 gene. It most likely acts upon caspase-3. CASP8 orthologs have been ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... For the death pathway, the caspase-8 zymogen is cleaved into subunits that assemble to form the mature, highly active caspase ...
Caspase-3 is a caspase protein that interacts with caspase-8 and caspase-9. It is encoded by the CASP3 gene. CASP3 orthologs ... As an executioner caspase, the caspase-3 zymogen has virtually no activity until it is cleaved by an initiator caspase after ... Caspase substrate specificity has been widely used in caspase based inhibitor and drug design. Caspase-3, in particular, (also ... During the caspase cascade, however, caspase-3 functions to inhibit XIAP activity by cleaving caspase-9 at a specific site, ...
... has been shown to interact with: Caspase 8, Survivin and XIAP. The Proteolysis Map Caspase GRCh38: Ensembl release 89 ... The precursor of this caspase is cleaved by caspase 3, caspase 10, and caspase 9. It is activated upon cell death stimuli and ... Caspases exist as inactive proenzymes that undergo proteolytic processing by upstream caspases (caspase-8, -9) at conserved ... Caspase-7 is a member of the caspase (cysteine aspartate protease) family of proteins, and has been shown to be an executioner ...
... initiating the caspase cascade. The activated caspases can go on to cleave intracellular proteins such as inhibitor of caspase- ... Activated caspase 8 cleaves these kinases, inhibiting necroptosis. Since activation of caspase 8 requires FADD in order to ... Caspase 8 then cleaves RIPK1, leading to inhibition of this signalling, inhibiting cell death. FADD knockout in mouse embryos ... FADD binds to ATG5 in a complex which also contains ATG12, Caspase 8 and RIPK1. The formation of this complex is stimulated by ...
Fas and Fas-ligand interact to trigger the caspase cascade, leading to cell apoptosis. Patients with ALPS have a defect in this ... Archived from the original on 2012-04-26.[unreliable medical source?] Van Der Werff Ten Bosch, Jutte; Schotte, Peter; Ferster, ... 20% of patients CEDS: Caspase 8 deficiency state. No longer considered a subtype of ALPS but distinct disorder RALD: NRAS, KRAS ... 2003 nomenclature IA - Fas IB - Fas ligand IIA - Caspase 10 IIB - Caspase 8 III - unknown IV - Neuroblastoma RAS viral oncogene ...
... has been shown to interact with Caspase 8. The Proteolysis Map Caspase GRCh38: Ensembl release 89: ENSG00000138794 - ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... Caspase 6 can also undergo self-processing without other members of the caspase family. Alternative splicing of this gene ... "Entrez Gene: CASP6 caspase 6, apoptosis-related cysteine peptidase". Cowling V, Downward J (Oct 2002). "Caspase-6 is the direct ...
"Entrez Gene: CARD10 caspase recruitment domain family, member 10". Wang L, Guo Y, Huang WJ, Ke X, Poyet JL, Manji GA, Merriam S ... Caspase recruitment domain-containing protein 10 is a protein in the CARD-CC protein family that in humans is encoded by the ... The caspase recruitment domain (CARD) is a protein module that consists of 6 or 7 antiparallel alpha helices. It participates ... "Card10 is a novel caspase recruitment domain/membrane-associated guanylate kinase family member that interacts with BCL10 and ...
Alcivar A, Hu S, Tang J, Yang X (Jan 2003). "DEDD and DEDD2 associate with caspase-8/10 and signal cell death". Oncogene. 22 (2 ... Alcivar A, Hu S, Tang J, Yang X (2003). "DEDD and DEDD2 associate with caspase-8/10 and signal cell death". Oncogene. 22 (2): ... Schickling O, Stegh AH, Byrd J, Peter ME (2002). "Nuclear localization of DEDD leads to caspase-6 activation through its death ... DEDD has been shown to interact with: CFLAR, Caspase 8, and FADD. GRCh38: Ensembl release 89: ENSG00000158796 - Ensembl, May ...
The function of caspase 4 is not fully known, but it is believed to be an inflammatory caspase, along with caspase 1, caspase 5 ... The Proteolysis Map Caspase Martinon F, Tschopp J (2007). "Inflammatory caspases and inflammasomes: master switches of ... Caspase 4 is an enzyme that proteolytically cleaves other proteins at an aspartic acid residue (LEVD-), and belongs to a family ... Smith C, Soti S, Jones Torey A, Nakagawa A, Xue D, and Yin H (2017). "NSAIDs are Caspase Inhibitors". Cell Chem Biol. 24 (3): ...
This caspase has been shown to be processed and activated by caspase 8 and caspase 10 in vitro, and by anti-Fas agonist ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... 1998). "Identification and characterization of murine caspase-14, a new member of the caspase family". Cancer Res. 58 (22): ... 2004). "Vitamin D3 induces caspase-14 expression in psoriatic lesions and enhances caspase-14 processing in organotypic skin ...
Instead, it is thought to inhibit Caspase-1 activation by interfering with the interaction of Caspase-1 with other important ... and a caspase, in this case Caspase-1. In some cases, where the signaling proteins contain their own CARDs, like in NLRP1 and ... Caspase-1 is produced as a zymogen that can then be cleaved into 20 kDa (p20) and 10 kDa (p10) subunits that become part of the ... Active Caspase 1 contains two heterodimers of p20 and p10. It contains a catalytic domain with an active site that spans both ...
It is an inflammatory caspase, along with caspase 1, caspase 4 and the murine caspase 4 homolog caspase 11, and has a role in ... The Proteolysis Map Caspase Martinon F, Tschopp J (2007). "Inflammatory caspases and inflammasomes: master switches of ... Caspase 5 is an enzyme that proteolytically cleaves other proteins at an aspartic acid residue, and belongs to a family of ... Caspases, All stub articles, Human chromosome 11 gene stubs). ...
Once activated, caspase-9 goes on to cleave caspase-3, -6, and -7, initiating the caspase cascade as they cleave several other ... Active caspase-9 works as an initiating caspase by cleaving, thus activating downstream executioner caspases, initiating ... Different protein isoforms of caspase-9 are produced due to alternative splicing. Similar to other caspases, caspase-9 has ... Previously activated caspases can cleave caspase-9, causing its dimerization. Caspase-9 has a preferred cleavage sequence of ...
CAD release from ICAD inhibition is achieved by cleavage of ICAD at these Asp residues by the caspase-3. Caspase-3 is activated ... Larsen BD, Rampalli S, Burns LE, Brunette S, Dilworth FJ, Megeney LA (March 2010). "Caspase 3/caspase-activated DNase promote ... October 2005). "The contribution of apoptosis-inducing factor, caspase-activated DNase, and inhibitor of caspase-activated ... "Entrez Gene: DFFB DNA fragmentation factor, 40kDa, beta polypeptide (caspase-activated DNase)". Davidson College. "Caspase ...
DR5 has been shown to interact with: Caspase 8, Caspase 10, FADD, and TRAIL. Monoclonal antibodies targeting DR5 have been ...
There are two types of caspases: initiators and effectors. Initiator caspases cleave inactive forms of effector caspases. This ... This pathway controls the activation of caspase-9 by regulating the release of cytochrome c from the mitochondrial ... Caspases (cysteine-aspartic acid proteases) cleave at very specific amino acid residues. ... each leading to the activation of caspase-9. The nucleus and Golgi apparatus are other organelles that have damage sensors, ...
... is a distinctive feature of DNA degraded by caspase-activated DNase (CAD), which is a key event during apoptosis ... Apoptotic DNA fragmentation Caspase-activated DNase Nicoletti assay TUNEL assay Wyllie AH (1980-04-10). "Glucocorticoid-induced ... caspase-3 activity by zinc supplementation in cultured HeLa cells". The Indian Journal of Medical Research. 129 (5): 579-586. ...
... is an initiator caspase, as are caspase-8 (EC, caspase-9 (EC and caspase-10 (EC ... Caspase-2 (EC, ICH-1, NEDD-2, caspase-2L, caspase-2S, neural precursor cell expressed developmentally down-regulated ... Caspase-2 at the US National Library of Medicine Medical Subject Headings (MeSH) Portal: Biology (EC 3.4.22). ... Li H, Bergeron L, Cryns V, Pasternack MS, Zhu H, Shi L, Greenberg A, Yuan J (August 1997). "Activation of caspase-2 in ...
Her research focuses especially on caspases, apoptotic proteins involved in the regulation of cell death, and with impacts in ... "Chemist Jeanne A. Hardy to Give Talk at Brookhaven Lab on Caspases, Causative Factor in Neurodegenerative Diseases , 4/24 , BNL ... Hardy, Jeanne A.; Wells, James A. (2009-07-06). "Dissecting an allosteric switch in caspase-7 using chemical and mutational ... Hardy's research group has determined allosteric regulation of caspase-6 selectively by zinc, mutation-based regulation of ...
In humans, initiator caspases such as Caspase-2 and Caspase-9 have a prodomain that cleaves caspases to a holoenzyme complex in ... In Drosophila melanogaster cells, caspase Dronc is ubiquitylated by Diap-1. Similarly, effector caspases Caspase-3 and Caspase- ... Just as caspase 9 in mammals, caspase Dronc is a protein that has a caspase activation and recruitment domain (CARD). It is the ... Although most human caspases are considered orthologs of caspase Dronc, the one that resembles it the most is Caspase-2. ...
... has been shown to interact with: Abl gene, CBX2, Caspase 10, E2F2, E2F3, Mdm2, RING1, and YY1. ENSG00000163602 GRCh38: ... 10 (2): 166-72. doi:10.1038/embor.2008.231. PMC 2637313. PMID 19098711. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, ...
It also selectively inhibits effector caspases 2, 3, 6, and 7 but not caspases 8 and 10. This compound has been shown to block ...
... caspase-11 (caspase-4 in humans), which is responsible for many of the effects previously attributed to caspase-1, including ... The 2011 paper showed that mice lacking the gene that encodes caspase-1 also carry a mutation in a neighboring caspase gene, ... They showed that these mechanisms did not depend on TLR4, but were rather mediated by caspase-11. This was significant, because ... By 2002, Dixit was among the first scientists to demonstrate that pro-inflammatory caspases are part of a molecular complex ...
McDonald ER, El-Deiry WS (2004). "Suppression of caspase-8- and -10-associated RING proteins results in sensitization to death ... 2005). "Crystal structure of a FYVE-type zinc finger domain from the caspase regulator CARP2". Structure. 12 (12): 2257-63. doi ... 15 (10): 4444-56. doi:10.1091/mbc.E04-04-0274. PMC 519139. PMID 15229288. "Entrez Gene: RFFL ring finger and FYVE-like domain ...
McDonald ER, El-Deiry WS (2004). "Suppression of caspase-8- and -10-associated RING proteins results in sensitization to death ... This protein can be cleaved by caspase-3 during the induction of apoptosis. Alternatively spliced transcript variants encoding ...
McDonald ER, El-Deiry WS (2004). "Suppression of caspase-8- and -10-associated RING proteins results in sensitization to death ... v t e (Articles with short description, Short description matches Wikidata, Genes on human chromosome 10, All stub articles, ... 2004). "The DNA sequence and comparative analysis of human chromosome 10". Nature. 429 (6990): 375-81. Bibcode:2004Natur.429.. ...
"Involvement of JNK and Caspase Activation in Hoiamide A-Induced Neurotoxicity in Neocortical Neurons". Mar. Drugs. 13 (2): 903- ...
Src (gene) has been shown to interact with the following signaling pathways: PI3K Akt IKK NFkB Caspase 9 STAT3 p38 MAPK VEGF IL ... 10 (3): 1000-9. doi:10.1128/mcb.10.3.1000. PMC 360952. PMID 1689455. Zan L, Wu H, Jiang J, Zhao S, Song Y, Teng G, Li H, Jia Y ... 1989-10-09. for their discovery of 'the cellular origin of retroviral oncogenes' Stehelin D, Fujita DJ, Padgett T, Varmus HE, ...
Wang M, Qanungo S, Crow MT, Watanabe M, Nieminen AL (2005). "Apoptosis repressor with caspase recruitment domain (ARC) is ... NOL3 has been shown to interact with SFRS9 and Caspase 8. GRCh38: Ensembl release 89: ENSG00000140939 - Ensembl, May 2017 ... Ekhterae D, Platoshyn O, Zhang S, Remillard CV, Yuan JX (2003). "Apoptosis repressor with caspase domain inhibits cardiomyocyte ... "Apoptosis repressor with caspase recruitment domain is required for cardioprotection in response to biomechanical and ischemic ...
Individuals suffering from TEN were found to have high concentrations of Granulysin in their blister fluid. Granulysin has also ... Granzymes usually cause apoptosis of the infected cell through initiation of the caspase cascade. However, apoptosis can also ... Granulysin plays a large role in Toxic Epidermal Necrolysis (TEN), a disease in which patients suffer from severe blistering, ... 169 (10): 5787-5795. doi:10.4049/jimmunol.169.10.5787. PMID 12421959. Ericson KG, Fadeel B, Andersson M, Gudmundsson GH, Gürgey ...
In brief, 20S sub complex presents three types proteolytic activities, including caspase-like, trypsin-like, and chymotrypsin- ... 29 (10): 2045-52. PMID 12375310. Coux O, Tanaka K, Goldberg AL (1996). "Structure and functions of the 20S and 26S proteasomes ... 12 (10): 1517-22. doi:10.1101/gr.418402. PMC 187523. PMID 12368243. Huang X, Seifert U, Salzmann U, Henklein P, Preissner R, ... 71: 3-10. doi:10.1016/j.yjmcc.2013.12.015. PMC 4011959. PMID 24380730. Drews O, Taegtmeyer H (Dec 2014). "Targeting the ...
... and caspase-dependent ATF5 degradation in hepatocellular carcinoma cells". The Journal of Biological Chemistry. 287 (23): 19599 ... 285 (10): 7827-7837. doi:10.1074/jbc.M109.040618. PMC 2844226. PMID 20053985. Nellist M, Burgers PC, van den Ouweland AM, ...
... called Inhibitor of caspase-activated DNase (ICAD). In order for apoptosis to begin, an enzyme called caspase 3 cleaves ICAD so ... "Caspase-activated DNase Is Required for Maintenance of Tolerance to Lupus Nuclear Autoantigens." Arthritis and Rheumatism 64.4 ... Apoptotic DNA fragmentation relies on an enzyme called Caspase-Activated DNase (CAD). CAD is usually inhibited by another ... "Identification of ICAD-derived Peptides Capable of Inhibiting Caspase-activated DNase." FEBS Journal 279.16 (2012): 2917-928. ...
"Galectin-9 induces apoptosis through the calcium-calpain-caspase-1 pathway". Journal of Immunology. 170 (7): 3631-6. doi: ... 169 (10): 5912-8. doi:10.4049/jimmunol.169.10.5912. PMID 12421975. Kashio Y, Nakamura K, Abedin MJ, Seki M, Nishi N, Yoshida N ... 207 (10): 2187-94. doi:10.1084/jem.20100643. PMC 2947065. PMID 20819927. Liu FT (April 2005). "Regulatory roles of galectins in ... 272 (10): 6416-22. doi:10.1074/jbc.272.10.6416. PMID 9045665. "Entrez Gene: LGALS9 lectin, galactoside-binding, soluble, 9 ( ...
Hayashi Y, Arakaki R, Ishimaru N (2003). "The role of caspase cascade on the development of primary Sjögren's syndrome". J. Med ... 10 (1-3): 3020-33. doi:10.2741/1759. PMID 15970557. Ursitti JA, Petrich BG, Lee PC, Resneck WG, Ye X, Yang J, Randall WR, Bloch ... 53 (6): e106-10. doi:10.1111/j.1528-1167.2012.03437.x. PMID 22429196. S2CID 20216273. Jain P, Spaeder MC, Donofrio MT, Sinha P ...
... activate inflammatory caspases (e.g. caspase 1) causing cleavage and activation of important inflammatory cytokines such as IL- ... Other NLRs such as IPAF and NAIP5/Birc1e have also been shown to activate caspase-1 in response to Salmonella and Legionella. ... 10 functional members of the TLR family have been described in humans so far. Studies have been conducted on TLR11 as well, and ... 10 (4): 971-982. doi:10.1038/mi.2016.98. PMC 5433921. PMID 27848951. Canning P, Ruan Q, Schwerd T, Hrdinka M, Maki JL, Saleh D ...
In cells, Bcl-rambo is localized to the mitochondria, and its overexpression induces apoptosis that is blocked by caspase ... 5 (10): R84. doi:10.1186/gb-2004-5-10-r84. PMC 545604. PMID 15461802. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, ...
In one such pathway, caspase-independent apoptosis, the E3 ligase C-terminal of Hsc-70 interacting protein (CHIP), a regulator ... Lemarié A, Lagadic-Gossmann D, Morzadec C, Allain N, Fardel O, Vernhet L (Jun 2004). "Cadmium induces caspase-independent ... This protein primarily participates in caspase-independent apoptosis via DNA degradation when translocating from the ... Differential involvement of caspase-3 and endonuclease G". Journal of Neurovirology. 10 (3): 141-51. doi:10.1080/ ...
Hsp70 member proteins, including Hsp72, inhibit apoptosis by acting on the caspase-dependent pathway and against apoptosis- ... 10 (1): 55-67. doi:10.1016/S1097-2765(02)00583-X. PMID 12150907. Ballinger CA, Connell P, Wu Y, Hu Z, Thompson LJ, Yin LY, ... 10 (5): e0128240. doi:10.1371/journal.pone.0128240. PMC 4444009. PMID 26010904. Kerr JF, Wyllie AH, Currie AR (Aug 1972). " ...
It has also been suggested that S1P kinase 2 (SphK2) is a target of caspase 1, and that a cleaved fragment of SphK2 is what is ... In other forms of apoptosis, caspase-1 is not normally induced, meaning the formation of S1P needs to be further studied. S1P ... S1P generation involved caspase-1-dependent release of sphingosine kinase 2 (SphK2) fragments. CX3CL1 release is mediated ... Release is dependent upon caspase activity. Less than 2% of ATP released from the beginning stages of cell death is released ...
2006). "Protein kinase WNK3 increases cell survival in a caspase-3-dependent pathway". Oncogene. 25 (30): 4172-82. doi:10.1038/ ... and it plays a role in the increase of cell survival in a caspase 3 dependent pathway. GRCh38: Ensembl release 89: ... 33 (10): 2250-3. doi:10.2337/dc10-0452. PMC 2945168. PMID 20628086. This article incorporates text from the United States ...
Such substrates have been used to detect caspase activity and cytochrome P450 activity, among others. Luciferase can also be ... Retrieved 2008-10-01. Nakamura M, Mie M, Funabashi H, Yamamoto K, Ando J, Kobatake E (May 2006). "Cell-surface-localized ATP ... The core part of the domain is a 10 stranded beta barrel that is structurally similar to lipocalins and FABP. The N-terminal ... In comparison, the incandescent light bulb only converts about 10% of its energy into light and a 150 lumen per Watt (lm/W) LED ...
Her demonstration that caspases are involved directly in ischaemic brain damage in vivo stimulated the development of caspase ... Abbit, Beth (10 September 2020). "Students could face exclusion if they flout social distancing rules, University of Manchester ... 2 (10): 734-744. doi:10.1038/35094583. PMID 11584311. S2CID 205020888. Denes, A.; Wilkinson, F.; Bigger, B.; Chu, M.; Rothwell ...
... encoding protein Caspase 16, pseudogene CCDC113: encoding protein Coiled-coil domain-containing protein 113 Ccdc78: encoding ... Miller, David T; Nasir, Ramzi; Sobeih, Magdi M; Shen, Yiping; Wu, Bai-Lin; Hanson, Ellen (2011-10-27). "16p11.2 Recurrent ...
... the apoptotic effector caspase, caspase 3, cleaves ICAD and thus causes CAD to become activated. CAD cleaves the DNA at the ... The enzyme responsible for apoptotic DNA fragmentation is the Caspase-activated DNase. CAD is normally inhibited by another ... "A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD". Nature. 391 (6662): 43-50. Bibcode: ... protein, the Inhibitor of Caspase Activated DNase (ICAD). During apoptosis, ...
2005). "Caspase-dependent and independent activation of acid sphingomyelinase signaling". J. Biol. Chem. 280 (28): 26425-26434 ... 2004). "Cathepsin D links TNF-induced acid sphingomyelinase to Bid-mediated caspase-9 and -3 activation". Cell Death Differ. 11 ... It was found that immediate hydrolysis of only 3 to 10% of newly generated ceramide may double the levels of Sph. Treatment of ...
"Induction of Caspase-9, Biochemical Assessment and Morphological Changes Caused by Apoptosis in Cancer Cells Treated with ... The smooth, elliptical, yellow to red fruit are 8-15 by 7.5-10 millimeters and have 1-2 seeds. The base of the fruit are wedge- ... It is a bush or small tree reaching 10 meters in height. Its moderately leathery leaves are 26-59 by 6-15.5 centimeters and ... The oval to narrowly elliptical outer petals are 10-28 by 4.5-11.5 millimeters. The outer petals are cream colored with pink ...
Mukerjee N, McGinnis KM, Gnegy ME, Wang KK (August 2001). "Caspase-mediated calcineurin activation contributes to IL-2 release ... 194 (10): 1449-59. doi:10.1084/jem.194.10.1449. PMC 2193671. PMID 11714752. Frey N, Olson EN (April 2002). "Calsarcin-3, a ...
... an investigational drug targeting caspases and caspase-like proteases: the clinical trials in sight and recent anti- ... May 2016). "The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute ... The substance acts as a pan-caspase inhibitor and has antiapoptotic and antiinflammatory effects. It was developed for the ... November 2005). "First-in-class pan caspase inhibitor developed for the treatment of liver disease". Journal of Medicinal ...
Once TRAIL is bound, Fas, caspase-8, and caspase-10 associate with the death domain forming death-inducing signaling complex ( ... The ORCTL3 gene spans around 12 kb of genomic DNA and consists of ten exons. It was shown that the 2.4 kb transcript of this ... In the absence of a viral infection, E4orf4 induces apoptosis in a p53 and caspase-independent manner; however, there is still ... In one cell type, DISC can directly activate the effector caspase leading to apoptosis, while in the other the complex ...
May 2012). "Influenza induces endoplasmic reticulum stress, caspase-12-dependent apoptosis, and c-Jun N-terminal kinase- ... at which point human procaspase 4 is believed to cause apoptosis by activating downstream caspases. Although PERK is recognised ... cytochrome c release and caspase 3 activation. Diseases Diseases amenable to UPR inhibition include Creutzfeldt-Jakob disease, ... Retrieved 2013-10-10. Blond-Elguindi S, Cwirla SE, Dower WJ, Lipshutz RJ, Sprang SR, Sambrook JF, Gething MJ (November 1993). " ...
... through the increase of caspase-3 and −8 activities". Ann N Y Acad Sci. 1010: 399-404. doi:10.1196/annals.1299.073. PMID ... Archived from the original on 10 August 2011. Retrieved 1 May 2012. (in Malay) Kehebatan budu Kelantan The Unique Cina Kampung ...
During early apoptotic signaling in human endothelial cells, FAK is cleaved by caspase 3 at Asp-772, generating two FAK ... 10 (3): 319-27. doi:10.1016/s0969-2126(02)00717-7. PMID 12005431. Lebrun P, Mothe-Satney I, Delahaye L, Van Obberghen E, Baron ... 10 (10): 722-34. doi:10.2174/187152010794728657. PMC 3274818. PMID 21291406. Researchers Stop Once-Promising Mesothelioma ...
The inactivation of RhoA acts an inducer of IL-1β mRNA transcription independent of NLRP3- or caspase-1 activity. Due to ... The gene which codes for mevalonate kinase consists of 10 exons at locus 12q14. About 63 pathological sequence variations in ...
BioVision develops and offers a wide variety of products including assay kits, antibodies, recombinant proteins & enzymes, and other innovative research tools for studying Apoptosis, Metabolism, Cell Proliferation, Cellular Stress, Cell Damage and Repair, Diabetes, Obesity and Metabolic Syndrome, Stem Cell Biology, Gene Regulation, Signal Transduction, etc. BioVisions products are currently being sold in more than 60 countries worldwide.
Caspase-2+Caspase-9+Caspase-8+Caspase-7+Caspase-1+Caspase-4+Caspase-6/CASP-6+Caspase-5+Caspase-10+Ca (1). ... Caspase-2+Caspase-9+Caspase-8+Caspase-7+Caspase-1+Caspase-6+Caspase-10+Caspase 3 (1). ... Caspase-3, Caspase-8 and Caspase-9 Multiplex Activity Assay Kit (Fluorometric) (ab219915) Specific References (16) ... Caspase-3, Caspase-8 and Caspase-9 Multiplex Activity Assay Kit (Fluorometric) ...
FASL:FAS Receptor Trimer:FADD:pro-Caspase-10 [plasma membrane] Stable Identifier ... FASL:FAS Receptor Trimer:FADD:pro-Caspase-10 [plasma membrane] (Homo sapiens) ... FASL:FAS Receptor Trimer:FADD:pro-Caspase-10 [plasma membrane] (Danio rerio) ... FASL:FAS Receptor Trimer:FADD:pro-Caspase-10 [plasma membrane] (Gallus gallus) ...
These inhibit caspase-3 and may affect a variety of other apoptosis and tumor related proteins. ... Caspase-3 Inhibitor Caspase-3 Inhibitor is an inhibitor of caspase-3, caspase-6, caspase-7, and caspase-10 210344-95-9 sc-3075 ... Caspase-3 Inhibitor I, Cell Permeable is an inhibitor of caspase-3, caspase-6, caspase-7, caspase-8, and caspase-10 sc-3074 1 ... Caspase-3/7 Inhibitor I Caspase-3/7 Inhibitor I is an inhibitor of caspase-3, caspase-7 and Caspase-9 220509-74-0 sc-293986 1 ...
This cascade eventually leads to the activation of the effector caspases, such as caspase 3 and caspase 6. These caspases are ... Caspases and the apoptosome. The caspases are a family of proteins that are one of the main executors of the apoptotic process ... Induction of apoptosis via death receptors typically results in the activation of an initiator caspase such as caspase 8 or ... Release of cytochrome C from mitochondria can lead to the activation of caspase 9, and then of caspase 3. This effect is ...
The substrate for caspase-3 was DEVD (Asp-Glu-Val-Asp), for caspase-6 - VEID (Val-Glu-Ile-Asp), for caspase-9 - LEНD (Leu-Glu- ... Note that the activity of caspase-6 in the cells (р,0.05) (Figure 5 b) treated with 4-NQO rose much less than that of caspases- ... Such are caspases. They are synthesized in the cell as precursors (procaspases). Caspase precursors consist of a prodomain and ... Caspases are a family of cysteine-dependent aspartate specific proteases. Caspases play an essential role in the apoptosis, ...
caspase regulator CARP2. caspases-8 and -10-associated RING finger protein 2. ring finger and FYVE-like domain containing 1. NP ... Common variants at ten loci influence QT interval duration in the QTGEN Study.. EBI GWAS Catalog. EBI GWAS CatalogPubMed ... FYVE_CARP2; FYVE-like domain found in caspase regulator CARP2 and similar proteins. cd16500. Location:315 → 353. RING-HC_CARP; ... Crystal structure of a FYVE-type zinc finger domain from the caspase regulator CARP2. Tibbetts MD, et al. Structure, 2004 Dec. ...
Research proven Caspase-3 (N terminal region) Rabbit Polyclonal IgG Antibody. Designed for immunohistochemistry, ... Caspase 3 is a heterotetramer of two heterodimers arranged in anti-parallel orientation. Caspase 3 activates caspases 6 and 7 ... CASP3 is a protein which is a member of the cysteine-aspartic acid protease (caspase) family. Caspase 3 participates in ... Caspase 3 in turn is processed by caspases 8, 9 and 10. ... Caspase-14. RA30061. 50 ug. Caspase-3 (C terminal region). ...
Upstream of the RNA helicase domain, both RIG-I and MDA5 have two N-terminal caspase recruitment domains (CARDs) that mediate ...
Caspase 10. Back to the top Specifications. Human CASP10 isoform D (longest) (pUNO1-hCASP10d). GenBank : NM_032977.3 with one ...
Caspase-3 Inhibitor II controls the biological activity of Caspase-3. This small molecule/inhibitor is primarily used for ... Primary Target: caspase-3, caspase-6, caspase-7, caspase-8, caspase-10 ... The InSolution™ Caspase-3 Inhibitor II controls the biological activity of Caspase-3. This small molecule/inhibitor is ... More,, The InSolution™ Caspase-3 Inhibitor II controls the biological activity of Caspase-3. This small molecule/inhibitor is ...
Caspases are intercellular proteases that are responsible for proteolytic cleavage. Caspase-3 is the main caspase that is ... caspase-3 and LDH levels. From the caspase 3 (apoptosis marker) test, apoptosis occurred at graphene doses ≥10 µg/mL. Thus, ... Zhang, L.; Sang, H.; Liu, Y.; Li, J. Manganese activates caspase-9-dependent apoptosis in human bronchial epithelial cells. Hum ... Increased ROS production can cause mitochondrial membrane depolarization and promote caspase activation. Mitochondrial membrane ...
... either caspase-8 or caspase-10. A family of viral and cellular proteins, known as FLIP, plays an essential role in the ... which culminates in the activation of the initiator caspase, ... either caspase-8 or caspase-10. A family of viral and cellular ... Strikingly, the overall packing arrangement between the two DEDs of MC159 resembles that between the caspase recruitment ... which culminates in the activation of the initiator caspase, ... domains of Apaf-1 and caspase-9. In addition, each DED of MC159 ...
Caspases play an important role as signal transducers (caspases 8, 9, 10) and as terminal executioners (caspases 3, 6, 7) in ... 20] Good neurologic outcomes were greatest when downtime was shortest: 62.5% at 10 minutes or less, 37% at 11-20 minutes, 25% ...
Mohr, A., Deedigan, L., Jencz, S., Mehrabadi, Y., Houlden, L., Albarenque, S-M. and Zwacka, RM., (2018). Caspase-10: a ... MOHR, A. and ZWACKA, R., (2007). In situ trapping of initiator caspases reveals intermediate surprises. Cell Biology ... and Zwacka, RM., (2003). 5-fluorouracil induced apoptotis inhuman colon cancer cells is mediated by caspase-8 and-2 and ... Mohr, A., Zwacka, RM., Schrezenmeier, H., Dohner, K., Wiesneth, M., Stahnke, K. and Debatin, KM., (2003). Caspase-8L expression ...
Caspase-1 activity was increased in SiO2- and, on a lesser scale, in TM- exposed cells. To test if the increased toxicity of TM ... Helmets were repeatedly impacted ten times using a commercial drop tower tester with an impactor (mass 3.6?kg) at different ... CytD blocked the uptake and significantly decreased cytotoxicity of all particles, while BafA prevented caspase-1 activation ... Asymptomatic CrAg-positive participants received preemptive fluconazole therapy for ten weeks. We assessed six-month survival ...
Caspase-3 (Pharmingen, San Diego, CA), caspase-8 (FADD-like interleukin-1 beta-converting enzyme) and caspase-9-like Mch6 (MBL ... The DN caspase-9 specifically blocked the cleavage of pro-caspase-9 in pcWNV-Cp-DJY and pcWNV-CpWT cotransfected cell lysates ... The cell lysates (100 μg/100 μl protein) were incubated with specific substrate Ac-DEVD-AMC for caspase-3, IETD-pNA for caspase ... Furthermore, to confirm that this apoptosis-induction pathway is through caspase-9, a domant negative (DN) caspase-9 construct ...
IL-18 and caspase-1 and the protein levels of Bcl-2, Bax, Bak1, caspase-3, NLRP3, caspase-1, GSDMD and IL-1β, but also increase ... Caspase-1 is activated by upstream inflammasome NLRP3 (Liu et al., 2018; Miao et al., 2011). Once activated, caspase-1 ... Pyroptosis is a caspase-1-dependent form of programmed inflammatory cell death. Apoptosis is a caspase-3-dependent and non- ... Noticeably, the mRNA levels of caspase-1 and IL-1β were changed differently in the two cell lines: the level of caspase-1 mRNA ...
Caspases, a family of cysteine acid proteases, are central regulators of apoptosis. Initiator caspases (including 8, 9, 10 and ... Once activated, these caspases cleave and activate downstream effector caspases (including 3, 6 and 7), which in turn cleave ... Cytochrome c released from mitochondria is coupled to the activation of caspase-9, a key initiator caspase (1). Proapoptotic ... DNA damage leads to the activation of caspase-9 and ER stress leads to the calcium-mediated activation of caspase-12 (3). The ...
Similarly, for the caspase assays, the general caspase inhibitor caspase inhibitor 3 (CI3; 25 μm; Calbiochem), the caspase-3 ... Ten minutes later, cultures were washed in leucine-containing medium (60% L15) (Invitrogen) and fixed with 25% TCA for 30 min. ... Caspase inhibitors. Caspase targets include actin and actin binding proteins, suggesting a possible mechanism by which caspases ... caspase inhibitor caspase-3 inhibitor CI3 and by the specific caspase-3-inhibitor C3I4 but not by an inhibitor of caspase-9, ...
... signaling by inhibiting a form of Bax that interrupts the caspase activation downstream of caspase-8 and upstream of caspase-9 ... Both the extrinsic and the intrinsic processes congregate at the activation of downstream effector caspases, (i.e., caspase-3 ... X. M. Sun, M. MacFarlane, J. Zhuang, B. B. Wolf, D. R. Green, and G. M. Cohen, "Distinct caspase cascades are initiated in ... In addition to Cyt-C, Smac/DIABLO as well as caspase independent death effectors inducing factor (AIF) and endonuclease G [171- ...
Genetic errors of the human caspase recruitment domain-B-cell lymphoma 10-mucosa-associated lymphoid tissue lymphoma- ... Patients Treated for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma by Helicobacter pyloriEradication and Followed for 10 ...
Activation of caspase-8 was rapidly followed by the appearance of caspase-3 activity in the cytoplasm ( Fig. 1a). ... We provide evidence that FADD and caspase-8, but not caspase-10, are recruited to the receptor. Moreover, mutant cell lines ... 1). Maximal recruitment of all proteins was observed after 30 min, at which time caspase-8 was converted from its precursor ... In contrast, the substantial amounts of caspase-10 detected in the cytoplasm were neither processed nor recruited to the DISC. ...
CRYSTAL STRUCTURE OF THE COMPLEX OF CASPASE-3 WITH A NICOTINIC ACID ALDEHYDE INHIBITOR ... Reducing the Peptidyl Features of Caspase-3 Inhibitors: A Structural Analysis.. Becker, J.W., Rotonda, J., Soisson, S.M., ... Caspases are cysteine proteases that specifically cleave Asp-Xxx bonds. They are key agents in inflammation and apoptosis and ... Caspases are cysteine proteases that specifically cleave Asp-Xxx bonds. They are key agents in inflammation and apoptosis and ...
A slow and caspase-independent apoptosis occurred in these cells after 8-10 days from the start of treatment. By contrast, a ... Eine Caspase-unabhängige Apoptose folgte in diesen Zellen erst nach 8-10 Tagen. Demgegenüber waren hMLH1--Zellen nicht komplett ...
... caspase 3, and caspase 9 in mammary tissues. Administration of genistein and lycopene in combination was more effective in ... NSAID Use Linked to Lower Rates of Breast Cancer - Doctors Guide, 7/15/03 - Ten years or more of ibuprofen use reduced a ... In addition, MGE induced apoptosis through enhancing the activities of caspase-3/7 by regulation of expression of Bcl-2, Bax, ... Furthermore, this study also observed that BDMC activated the caspase 3/9 signaling pathway to induce TNBC apoptosis. Therefore ...
Can NucView™ 488 Caspase-3 Substrate be used for tissue staining?. FAQ from biotium. NucView™ 488 Caspase-3 Substrate has not ... Using NucView™ 488 Caspase-3 Substrate for tissue staining?. by Interchim » Fri 6 Feb 2015 18:18 ... Board index ‹ LIFE SCIENCES , BIOSCIENCES ‹ CELL BIOLOGY ‹ NucView 488 Caspase 3 enzyme substrate FAQ ... Using NucView™ 488 Caspase-3 Substrate for tissue staining?. Moderator: Interchim LSciences ...
... and caspase-dependent (caspase-3/8/9) cell death pathway. It upregulated the expression of pro-apoptotic Bax and downregulated ... Caspase-8 activation was correlated with the decrease in the levels of cellular FLICE-inhibitory protein (c-FLIP), an inhibitor ... Elemene induced caspase-3, -7, and -9 activities, decreased Bcl-2 expression, resulted in cytochrome c release and increased ... There was an apoptotic trigger which was an outcome of the activation of caspases-3, -8, and -9, the loss of mitochondrial ...
... live cell caspases activity assay kits are based on fluorescent FMK inhibitors of caspases Cat No. 20108 ... Once inside the cell, the caspase inhibitors bind covalently to the active caspases. This Cell Meter™ Live Cell Caspase 1 ... Cell Meter™ Caspase 8 Activity Apoptosis Assay Kit *Red Fluorescence*. Cell Meter™ Caspase 9 Activity Apoptosis Assay Kit *Red ... Cell Meter™ Caspase 3/7 Activity Apoptosis Assay Kit *Blue Fluorescence*. Cell Meter™ Caspase 3/7 Activity Apoptosis Assay Kit ...
This apoptosome recruits and activates caspase-9, which in turn activates the executioner caspases, caspase-3 and caspase-7 (7 ... They activate caspase-dependent cell death pathways by suppressing the ability of IAPs to inhibit caspases. It has been shown ... SmacN7 disrupted binding of XIAP to processed caspase-9 and then initiated caspase-3 processing in H460 cells but had little ... These findings suggest that SmacN7(R)8 potentiates caspase-independent cell death by taxol as well as caspase-dependent cell ...
  • Caspase family members function as key components of the apoptotic machinery and act to destroy specific target proteins which are critical to cellular longevity. (scbt.com)
  • Caspase-3 Inhibitors offered by Santa Cruz inhibit caspase-3 and, in some cases, other apoptosis and tumor related proteins. (scbt.com)
  • The caspases are a family of proteins that are one of the main executors of the apoptotic process. (reading.ac.uk)
  • These caspases are responsible for the cleavage of the key cellular proteins, such as cytoskeletal proteins, that leads to the typical morphological changes observed in cells undergoing apoptosis. (reading.ac.uk)
  • The caspases play an important role in this process by activating DNases, inhibiting DNA repair enzymes and breaking down structural proteins in the nucleus. (reading.ac.uk)
  • The enzyme poly (ADP-ribose) polymerase, or PARP, was one of the first proteins identified as a substrate for caspases. (reading.ac.uk)
  • Depending on the phase at which those proteins enter the apoptotic cascade one distinguishes initiator (apical) and effector (executioner) caspases. (intechopen.com)
  • The results showed that BPA nonlinearly upregulated the levels of IL-18, ASC, GSDMD and NLRP3 mRNAs and that of NLRP3, caspase-1, GSDMD and IL-1β proteins in IMR-32 and SK-N-SH cells. (researchsquare.com)
  • Meanwhile, Z-YVAD-FMK and ICI182.780 abruptly reduced the levels of Bak1, Bax, Bcl-2 and caspase-3 proteins induced by BPA. (researchsquare.com)
  • Etoposide treatment induces proteolytic cleavage of various apoptosis-related proteins including caspases, IAP, and PARP. (cellsignal.com)
  • Once activated, these caspases cleave and activate downstream effector caspases (including 3, 6 and 7), which in turn cleave cytoskeletal and nuclear proteins like PARP, α-fodrin, DFF and lamin A, and induce apoptosis. (cellsignal.com)
  • The most important of them are the porins, which freely allow the transport (export and import) of the molecules (proteins, ions, nutrients, and ATP) less than 10 kDa across the membranes. (hindawi.com)
  • Proteins destined to mitochondria have either internally localized [ 28 ] or amino terminal localized [ 21 ] presequences known as mitochondria/matrix localization signals (MLS), which can be 10-80 amino acid long with predominantly positively charged amino acids. (hindawi.com)
  • BJAB cells express TRAIL-R1 and TRAIL-R2 complementary DNA [14], and both TRAIL-receptor proteins were incorporated into the DISC, along with FADD and caspase-8, after 5 min of stimulation (Fig. 1). (gale.com)
  • Maximal recruitment of all proteins was observed after 30 min, at which time caspase-8 was converted from its precursor into the active processed form, as shown by the appearance of the p43 fragment [12] in the DISC. (gale.com)
  • The inhibitor of apoptosis proteins (IAPs) plays a central role in repressing caspase-mediated cell death. (aacrjournals.org)
  • The note of positive feedback is supported by an observation on the kinetics of changes of all relevant proteins in which cleavage of both caspase 10 and Mcl-1 were found to be late events. (cdc.gov)
  • Down-regulation of important metabolic, detoxification and immunregulatory proteins was associated with induction of endoplasmic reticulum stress (ER) in IEC of IL-10-/- mice under pathologic conditions. (tum.de)
  • Caspases are tightly regulated proteins that require zymogen activation to become active, and once active can be regulated by caspase inhibitors. (embl.de)
  • At the end of the cascade, caspases act on a variety of signal transduction proteins, cytoskeletal and nuclear proteins, chromatin-modifying proteins, DNA repair proteins and endonucleases that destroy the cell by disintegrating its contents, including its DNA. (embl.de)
  • Several families of proteins including the Bcl-2, tumor necrosis factor receptor 1, and caspase families play essential roles in the regulation, signaling, and execution of the genetic cell death program. (embl.de)
  • Once activated, caspases -3 and -7 cleave downstream proteins. (smpdb.ca)
  • The robust proapoptotic activity was found to be the consequence of a positive feedback mechanism-governed amplification of caspase activation and cleavage of both Mcl-1 and Akt proteins, and exhibited a relative selectivity in MPM cells than in non-tumorigenic Met-5A mesothelial cells. (cdc.gov)
  • View detailed caspase-3 Inhibitor specifications, including caspase-3 Inhibitor CAS number, molecular weight, molecular formula and chemical structure, by clicking on the product name. (scbt.com)
  • Q-VD-OPH is a low toxicity broad-spectrum inhibitor of caspase-3, caspase-1, caspase-8 and caspase-9. (scbt.com)
  • PKR Inhibitor inhibits RNA-induced PKR autophosphorylation, as well as caspase-3 and caspase-8, and prevents increases in pT(451)-PKR and pS(194)-FADD levels in SH-SY5Y nuclei. (scbt.com)
  • The InSolution™ Caspase-3 Inhibitor II controls the biological activity of Caspase-3. (merckmillipore.com)
  • The inhibitor of apoptosis protein (IAP) family includes XIAP and survivin and functions by binding and inhibiting several caspases (4,5). (cellsignal.com)
  • This in vitro assay employs the fluorescent inhibitor probe FAM-LETD-FMK to label active caspase-8 enzyme in living cells. (immunochemistry.com)
  • The presence of Ac-DEVD-CHO (a caspase-3 inhibitor) markedly enhanced the potency of TL04 in improving the viability of glutamate-exposed DPC12 cells. (spandidos-publications.com)
  • Pharmacological p-38 MAPK inhibitor blocked IL-10-mediated inhibition of ATF6 recruitment to grp-78 promoter in TNF-stimulated IL-10-receptor reconstituted Mode-K cells suggesting the involvement of p-38 MAPK signalling in regulation of ER-stress response. (tum.de)
  • This cascade eventually leads to the activation of the effector caspases, such as caspase 3 and caspase 6. (reading.ac.uk)
  • caspase-3, -6, -7 - effector ones. (intechopen.com)
  • Under certain conditions effector caspases may act as initiator ones to accelerate apoptotic reactions. (intechopen.com)
  • In H460 cells, the overexpressed XIAP, but not c-IAP1, bound to the processed form of caspase-9 and suppressed the activation of downstream effector caspases. (aacrjournals.org)
  • A long pro-domain caspase that contains a death effector domain in its pro-domain region. (bvsalud.org)
  • Caspase 10 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES . (bvsalud.org)
  • Caspase-8 is an initiator caspase that is activated in response to pro-apoptotic stimulus and causes a cascade of further caspase activity by cleaving and activating effector caspases, like caspases -3 and -7. (smpdb.ca)
  • A short pro-domain caspase that plays an effector role in APOPTOSIS . (nih.gov)
  • This effect is mediated through the formation of an apoptosome, a multi-protein complex consisting of cytochrome C, Apaf-1, pro-caspase 9 and ATP. (reading.ac.uk)
  • Initiator caspase activation is more sophisticated - by special protein complexes: apoptosomes, PIDDosomes, DISC ( death-inducing signalling complexes ) [ 7 , 8 ]. (intechopen.com)
  • CASP3 is a protein which is a member of the cysteine-aspartic acid protease (caspase) family. (neuromics.com)
  • Caspase 3 participates in cleavage of Amyloid beta 4A precursor protein which is implicated with neuronal death Alzheimer's disease. (neuromics.com)
  • We observed that the WNV-Cp protein is a pathogenic protein, which drives apoptosis in vitro through the mitochodrial/caspase-9 pathway. (cdc.gov)
  • For a caspase-9-specific test, 5 μg of pcWNV-Cp-DJY or pcWNV-CpWT was cotransfected with a dominant negative caspase-9 (DN caspase-9) construct, and cleavage of procaspase-9 protein was determined by Western blot analysis with antihuman caspase-9 antibody (MBL, Nagoya, Japan). (cdc.gov)
  • Smac/Diablo, a mitochondrial protein, is released into the cytosol upon mitochondrial stress and competes with caspases for binding of IAPs. (cellsignal.com)
  • Similar inhibition of growth cone formation was observed on addition of target of rapamycin (TOR), p38 MAPK (mitogen-activated protein kinase), and caspase-3 inhibitors. (jneurosci.org)
  • Collectively, these findings suggest that local protein synthesis and degradation, controlled by various TOR-, p38 MAPK-, and caspase-dependent pathways, underlie growth cone initiation after axotomy. (jneurosci.org)
  • Collectively, this study demonstrates that culmination of MG132-induced apoptosis depends on a positive feedback for an enhanced caspase activation which converts Mcl-1 from an anti-apoptotic protein into a proapoptotic protein. (cdc.gov)
  • Caspase 8 antibody detects Caspase 8 protein at cytoplasm by immunofluorescent analysis. (genetex.com)
  • Protein expression profiling was performed in native IEC isolated from colonic tissue of wild type and IL-10-/- mice after 2 and 14 weeks of monoassociation with E. faecalis. (tum.de)
  • Consistent with the presence of histopathology and persistent TLR2-mediated NF-B activation in IEC of IL-10-/- mice, proteome analysis revealed divergent protein expression changes between WT and IL-10-/- mice at early and late colonization time points. (tum.de)
  • Specific gene targeting of another protein galectin-3 in Mode-K cell line resulted in the induction of cleaved caspase-3, suggesting anti-apoptotic functions of this protein in IEC. (tum.de)
  • Thus, protein expression profiling in native IEC revealed involvement of ER-stress, energy depletion and disturbance of mitochondrial homeostasis in the pathogenesis of experimental colitis in IL-10-/- mice. (tum.de)
  • Fas ligand binds to the receptor and forms the death-inducing signalling complex, including the Fas-associated death domain, death-domain associated protein, and caspase-10. (smpdb.ca)
  • The anti proliferative properties of the C. morifolia petroleum ether extract turned out to be attributable to the induction of cell death as the apoptotic executioner protein caspase 3 was already activated within 2 hours of incubation. (univie.ac.at)
  • Around the same time, we and others described a protein that we initially termed Acrp30, which later became known as adiponectin ( 7 - 10 ). (diabetesjournals.org)
  • Caspase 3, Apoptosis-Related Cysteine Peptidase (aa 176-277) Protein, tagged with His tag. (creative-biolabs.com)
  • Santa Cruz Biotechnology now offers a broad range of caspase-3 Inhibitors. (scbt.com)
  • We present seven crystal structures of inhibited caspase-3 that illustrate several approaches to reducing the peptidyl characteristics of the inhibitors while maintaining their potency and selectivity. (rcsb.org)
  • Our Cell Meter™ live cell caspases activity assay kits are based on fluorescent FMK inhibitors of caspases. (aatbio.com)
  • Once inside the cell, the caspase inhibitors bind covalently to the active caspases. (aatbio.com)
  • It is used for the quantification of activated caspase 1 activities in apoptotic cells, or for screening caspase 1 inhibitors. (aatbio.com)
  • Inhibition of caspases 3 and 9 by either specific caspase inhibitors or corresponding siRNAs inhibited MG132-induced apoptosis and PARP cleavage. (cdc.gov)
  • Caspases are a family of cysteine-dependent aspartate specific proteases. (intechopen.com)
  • Caspases, a family of cysteine acid proteases, are central regulators of apoptosis. (cellsignal.com)
  • Caspases are cysteine proteases that specifically cleave Asp-Xxx bonds. (rcsb.org)
  • Caspase family of cysteine proteases has been shown to play a key role in apoptosis. (anobase.org)
  • Activated caspases act as cysteine proteases, using the sulphydryl group of a cysteine side chain for catalysing peptide bond cleavage at aspartyl residues in their substrates. (embl.de)
  • Caspases are are proteases that cleave their substrates. (smpdb.ca)
  • Caspases are cysteine proteases involved in the signalling cascades of programmed cell death in which caspase-3 plays a central role, since it propagates death signals from intrinsic and extrinsic stimuli to downstream targets. (proteopedia.org)
  • The ability of PARP to repair DNA damage is prevented following cleavage of PARP by caspase-3. (reading.ac.uk)
  • All caspases are originally inactive, but activated when needed by cleavage of a small fragment by initiator caspases. (intechopen.com)
  • Culmination of MG132-induced apoptosis in human lung cancer NCI-H1703 cells depends on a positive feedback of caspase activation and Mcl-1 cleavage. (cdc.gov)
  • It was observed that MG132 concentrations of greater than 0.25 µM caused a significant apoptosis as evidenced by DNA damage, cleavage of caspases 3, 7, 9, 10, Bid and PARP, and mitochondrial release of Smac/DIABLO and Cytochrome c. (cdc.gov)
  • It also inhibited cleavage of caspase 10 and Bid, mitochondrial release of Smac/DIABLO and reduction of Mcl-1 to higher dosages of MG132, suggesting the existence of a positive feedback in caspase activation by the initially activated caspases 3 and 9, which leads to further activation of caspases 3 and 9 through caspase 10 and the mitrochondria. (cdc.gov)
  • Caspases cleave nuclear lamins, causing the nucleus to break down and lose its normal structure and another caspase substrate is DFF, inducing cleavage and degradation of the genome. (prospecbio.com)
  • Cabrera JR, Bouzas-Rodriguez J, Tauszig-Delamasure S, Mehlen P. RET modulates cell adhesion via its cleavage by caspase in sympathetic neurons. (proteopedia.org)
  • The fragmentation of DNA into nucleosomal units - as seen in DNA laddering assays - is caused by an enzyme known as CAD, or caspase activated DNase. (reading.ac.uk)
  • The remaining green fluorescent signal is a direct measure of the active caspase-8 enzyme activity present in the cell at the time the reagent was added. (immunochemistry.com)
  • Over expression of interleukin-1β-converting enzyme (later renamed caspase-1) was shown to be sufficient to induce apoptosis in mammalian cells. (who.int)
  • the expression of specific CNS enzyme (enolase), proinflammatory cytokines MIF and apoptotic marker caspase-3 in the umbilical blood of infants delivered for Covid positive mothers. (who.int)
  • Using pharmacological inhibition of apoptosis-associated caspases, we find evidence that apoptosis eliminates hitherto undiscovered rudiments of the lateral line sensory system which, in fish and aquatic amphibia, serves to detect movements, pressure changes or electric fields in the surrounding water. (biologists.com)
  • In addition, we found that IL-10 was able to down-regulate transcriptional activity of grp-78 via the inhibition of ATF6 nuclear translocation and binding to the grp-78 promoter. (tum.de)
  • The stimulation or inhibition of different Bcl-2 family receptors results in the leakage of cytochrome c from the mitochondria, and the formation of an apoptosome composed of cytochrome c, Apaf1 and caspase-9. (embl.de)
  • 10 MK-8776 inhibition Roughly,000 cells had been analyzed per test. (ecologicalsgardens.com)
  • Outcomes HHT and ETP display synergistic cytotoxicity in AML cells ETP and HHT are cytotoxic reagents for AML cells.21,22 To check whether ETP and HHT possess synergistic cytotoxicity in AML cells, the chemosensitive AML super model tiffany livingston cell lines (THP1 MK-8776 inhibition and HL60) were treated with HHT and ETP alone or in combination (10/1 and 20/2, nM/M) for 48 hours. (ecologicalsgardens.com)
  • Apoptosis is induced through the mitochondrial pathway resulting in caspase-9 activation and downstream caspase-3 activation. (cdc.gov)
  • Caspase-8 and caspase-10 are first activated, to then cleave and activate downstream caspases, and a variety of cellular substrates that lead to cell death. (prospecbio.com)
  • Other caspase substrates are involved in cytoskeletal structure, cell cycle regulation and signaling pathways. (prospecbio.com)
  • Induction of apoptosis via death receptors typically results in the activation of an initiator caspase such as caspase 8 or caspase 10. (reading.ac.uk)
  • Death receptor signaling is initiated by the assembly of the death-inducing signaling complex, which culminates in the activation of the initiator caspase, either caspase-8 or caspase-10. (nih.gov)
  • Initiator caspases (including 8, 9, 10 and 12) are closely coupled to proapoptotic signals. (cellsignal.com)
  • Cytochrome c released from mitochondria is coupled to the activation of caspase-9, a key initiator caspase (1). (cellsignal.com)
  • It is activated by INITIATOR CASPASES such as CASPASE 3 and CASPASE 10 . (nih.gov)
  • Using NucView™ 488 Caspase-3 Substrate for tissue staining? (interchim.com)
  • NucView™ 488 Caspase-3 Substrate has not been validated by Biotium for live tissue staining. (interchim.com)
  • However, we have had feedback from a customer who successfully used NucView™ 488 Caspase-3 Substrate for live zebrafish embryo staining. (interchim.com)
  • NucView™ 488 Caspase-3 Substrate cannot be used in fixed cells or tissues. (interchim.com)
  • , Boyd, SE , Salvesen, GS & Arampatzidou, M (ed.) 2007, ' Histone deacetylase 7 is a caspase-8 substrate ', General Meeting of the International Proteolysis Society 2007, Basel Switzerland, 20/10/07 - 24/10/07 pp. 283 - 283. (monash.edu)
  • The atomic resolution (1.06 Angstroms) crystal structure of the caspase-3 DEVD-cmk complex reveals the structural basis for substrate selectivity in the S4 pocket. (proteopedia.org)
  • Ganesan R, Mittl PR, Jelakovic S, Grutter MG. Extended substrate recognition in caspase-3 revealed by high resolution X-ray structure analysis. (proteopedia.org)
  • This Cell Meter™ Live Cell Caspase 1 Activity Assay Kit is designed to detect cell apoptosis by measuring caspase 1 activation in live cells. (aatbio.com)
  • Detect caspase-8 activity with the FLICA Caspase-8 Assay Kit. (immunochemistry.com)
  • Bulk Order Inquiry for FAM-FLICA® Caspase-8 Assay Kit ------- (please add any order requirements, including desired quantity, timing, etc. (immunochemistry.com)
  • ICT's FLICA assay kits are used by researchers seeking to quantitate apoptosis via caspase activity in cultured cells and tissues. (immunochemistry.com)
  • The FAM FLICA Caspase-8 assay probe allows researchers to assess caspase-8 activation. (immunochemistry.com)
  • Caspase 3/7 activity assay Cells had been plated as referred to for cell viability and treated with raising concentrations of TM5275 or TM5441 for 48 hours. (exposed-skin-care.net)
  • Cells were fixed with 1% formaldehyde incubated with rabbit polyclonal antibody to N-terminal region of Caspase 3 at 6 μg/mL overnight at 4°C followed by incubation with Donkey anti-rabbit Rhodamine Red conjugated secondary antibodies at 1:200 dilution. (neuromics.com)
  • Western blot analysis of Jurkat Apoptosis Cell Extracts #2043 using Caspase-7 Antibody, #9492. (cellsignal.com)
  • The immunogen used to generate this antibody corresponds to dog Caspase 8. (genetex.com)
  • Green: Caspase 8 stained by Caspase 8 antibody (GTX134950) diluted at 1:100. (genetex.com)
  • Whole cell extract (30 μg) was separated by 10% SDS-PAGE, and the membrane was blotted with Caspase 8 antibody (GTX134950) diluted at 1:1000. (genetex.com)
  • There are currently no references for Caspase 8 antibody - VetSignal (GTX134950) . (genetex.com)
  • These caspases can then activate other caspases in a cascade. (reading.ac.uk)
  • There are a number of other mechanisms, aside from activation of the death receptors, through which the caspase cascade can be activated. (reading.ac.uk)
  • The mitochondria are also key regulators of the caspase cascade and apoptosis. (reading.ac.uk)
  • DN caspase-9 (provided courtesy of Emad S. Alnmeri, Thomas Jefferson University, Philadelphia, PA) has been reported to inhibit the caspase cascade ( 5 ). (cdc.gov)
  • Binding of FAS to oligimerized FasL on another cell activates apoptotic signaling through a cytoplasmic domain termed the death domain that interacts with signaling adaptors including FAF, FADD and DAX to activate the caspase proteolytic cascade. (prospecbio.com)
  • The subsequent activation of caspase-8 initiates the apoptosis cascade involving caspases 3, 4, 6, 7, 9 and 10. (embl.de)
  • CASP3_HUMAN ] Involved in the activation cascade of caspases responsible for apoptosis execution. (proteopedia.org)
  • Release of cytochrome C from mitochondria can lead to the activation of caspase 9, and then of caspase 3. (reading.ac.uk)
  • Caspase 3 activates caspases 6 and 7 and this sequential activation leads to apoptosis. (neuromics.com)
  • Fas and TNFR activate caspases 8 and 10 (2), DNA damage leads to the activation of caspase-9 and ER stress leads to the calcium-mediated activation of caspase-12 (3). (cellsignal.com)
  • Activation of caspase-8 was rapidly followed by the appearance of caspase-3 activity in the cytoplasm ( Fig. 1a). (gale.com)
  • DNA fragmentation and activation of caspases are the major hallmarks of apoptosis ( Saraste and Pulkki, 2000 ). (frontiersin.org)
  • We found that the cytochrome c /apoptotic protease-activating factor-1 (apoptosome)-dependent caspase activation is deficient in human non-small cell lung cancer (NSCLC) NCI-H460 cells. (aacrjournals.org)
  • Induction of apoptosis via caspase activation is believed to be the major mechanism of PIs' ability to kill cancer cells. (cdc.gov)
  • Activation of caspases can be mediated by other caspase homologues. (embl.de)
  • The activation of apoptosis can sometimes lead to caspase-1 activation, providing a link between apoptosis and inflammation, such as during the targeting of infected cells. (embl.de)
  • Recent advances have indicated that inflammasomes contribute the etiology of MS. Inflammasomes are multiprotein complexes of the innate immune response involved in the processing of caspase-1, the activation of pro-inflammatory cytokines interleukin (IL)-1β and IL-18 as well as the cell death-mediated mechanism of pyroptosis and the activation of the adaptive immune response. (springer.com)
  • Organic solvent-induced proximal tubular cell toxicity via caspase-3 activation. (cdc.gov)
  • Store at -20°C. Supplied in SDS Sample Buffer: 62.5 mM Tris-HCl (pH 6.8 at 25°C), 2% w/v SDS, 10% glycerol, 50 mM DTT, 0.01% w/v bromophenol blue or phenol red. (cellsignal.com)
  • 100 mM NaCL, 20 mM Hepes, 10% glycerol. (creative-biolabs.com)
  • CDDO-Me significantly decreased B-cell lymphoma-extra large (Bcl-xl), B-cell lymphoma 2 (Bcl-2), cleaved caspase-9, and cleaved poly ADP ribose polymerase (PARP) levels but increased the expression level of Bcl-2-associated X (Bax). (dovepress.com)
  • However, whereas 10- 20 ng/ml TRAIL alone induced a limited apoptosis as well, TRAIL and PI combination triggered a robust apoptosis in all three MPM cell lines. (cdc.gov)
  • During apoptosis, different caspases perform different functions. (intechopen.com)
  • The different caspases have different domain architectures depending upon where they fit into the apoptosis cascades, however they all carry the catalytic p10 and p20 subunits. (embl.de)
  • Experiments demonstrate that the reduction of mitochondrial membrane potential (MMP, Δψ m) leads to the release of cytochrome c (Cyto C), whose cytoplasmic localization initiates caspase-dependent apoptotic cell death. (spandidos-publications.com)
  • The identification of caspases as major regulators of apoptotic cell death in animals initiated a quest for homologous peptidases in other kingdoms. (rupress.org)
  • As mediated by the estrogen receptor, BPA may induce the pyroptosis of neuroblastoma cells through NLRP3/caspase-1/GSDMD signaling pathway, and caspase-1-dependent pyroptosis may be involved in BPA-induced apoptosis, which is alleviated by EGCG, an anti-oxidation agent. (researchsquare.com)
  • He, L;Wei, T;Huang, Y;Zhang, X;Zhu, D;Liu, H;Wang, Z. miR-214-3p Deficiency Enhances Caspase-1-Dependent Pyroptosis of Microglia in White Matter Injury . (immunochemistry.com)
  • P2X7 stimulation promotes caspase-mediated pyroptosis of Tfh cells and controls the development of pathogenic ICOS + IFN-γ-secreting cells. (elsevier.com)
  • Collectively, the results demonstrated that the purified polysaccharides separated from Tremella fuciformis (TL04) possess a neuroprotective effect against glutamate-induced DPC12 cell damage predominantly through the caspase-dependent mitochondrial pathway. (spandidos-publications.com)
  • To investigate the effects of Banxia Houpo decoction on the renal NLRP3/Caspase-1/IL-1β signaling pathway in chronic intermittent hypoxia mice. (magtech.com.cn)
  • Granzyme B can be delivered into cells by cytotoxic T lymphocytes and is able to directly activate caspases 3, 7, 8 and 10. (reading.ac.uk)
  • Degradation of lamins by caspase 6 results in the chromatin condensation and nuclear fragmentation commonly observed in apoptotic cells. (reading.ac.uk)
  • Immunohistochemical detection of Caspase 3 in apoptosis induced Jurkat cells. (neuromics.com)
  • Noticeably, the mRNA levels of caspase-1 and IL-1β were changed differently in the two cell lines: the level of caspase-1 mRNA was enhanced in IMR-32 cells but suppressed in SK-N-SH cells, and that of IL-1β was suppressed in IMR-32 cells but enhanced in SK-N-SH cells. (researchsquare.com)
  • A slow and caspase-independent apoptosis occurred in these cells after 8-10 days from the start of treatment. (fu-berlin.de)
  • FAM-YVAD-FMK, the green label reagent, allows for direct detection of activated caspase 1 in apoptotic cells by fluorescence microscopy, flow cytometer, or fluorescent microplate reader. (aatbio.com)
  • Culture cells to a density optimal for apoptosis induction according to your specific induction protocol, but not to exceed 2 x 10 6 cells/ mL. (aatbio.com)
  • The cells can be concentrated up to ~ 5 X 10 6 cells/mL for FAM-YVAD-FMK labeling. (aatbio.com)
  • Add diluted FLICA to each sample at 1:30 (e.g., add 10 μL to 290 μL of cultured cells). (immunochemistry.com)
  • We showed that intestinal epithelial cells (IEC) of IL-10-/- mice lack protective TGFSmad signalling and fail to inhibit expression of NF-B-dependent genes of pro-inflammatory cytokines. (tum.de)
  • For BrdU incorporation, cells had been pulsed with 10 M BrdU for 20 mins before being gathered using the fluorescein isothiocyanate (FITC) BrdU Movement kit (BD) based on the producers suggestions. (exposed-skin-care.net)
  • For calculating ROS level, cells had been treated with 10 M H2DCFH-DA for thirty minutes at night, followed by 2 times cleaning with PBS. (ecologicalsgardens.com)
  • In lean adipose tissue, IL-4 secreted by eosinophils and Th2 cells activates M2 type macrophages, which express arginase and anti-inflammatory cytokines such as IL-10. (molcells.org)
  • Regulatory T (Treg) cells also play an important role in anti-inflammatory responses via cell-cell contact or cytokine secretion involving IL-10. (molcells.org)
  • ABL-N administration induced apoptosis of PC3 cells in a dose-dependent manner, along with the enhanced activity of caspases and increased Bax/Bcl-2 ratio. (cusabio.com)
  • Caspase-8 activity is regulated by CASP8 and FADD-like apoptosis regulator. (smpdb.ca)
  • As of now, at lease 14 caspases have been described from mammals: 8 caspases are involved in apoptosis, 5 activate anti-inflammatory cytokines, and one acts in keratinocyte differentiation. (intechopen.com)
  • The FLICA reagent FAM-LETD-FMK enters each cell and irreversibly binds to activated caspase-8. (immunochemistry.com)
  • On average, dengue becomes symptomatic after a 4- to 10-day incubation period (range, 3-14 days). (medscape.com)
  • An extrinsic physiological abnormality being an acute increase incubation period of 8-10 days is required in vascular permeability leading to extravasation before the virus appears in the saliva of the of fluid, haemoconcentration and hypotension. (who.int)
  • Exhibits little inhibitory effect against active caspase-7 (30 nM) even at concentrations as high as 50 µM, nor does it activate procaspase-1 or -7 even after prolonged incubations upto 4 and 24 h, respectively. (merckmillipore.com)
  • Western blot analysis of Jurkat Apoptosis Cell Extracts #2043 using Caspase-3 (8G10) Rabbit mAb, #9665. (cellsignal.com)
  • Load 10 µl of untreated and etoposide treated Jurkat Apoptosis Control Cell Extracts (etoposide) per lane. (cellsignal.com)
  • Moreover, mutant cell lines that lack FADD or caspase-8 are resistant to TRAIL-induced death. (gale.com)
  • A cell-permeable phenylimidazopyridinyl-methoxy coumarin compound that inhibits caspase-3 and caspase-6 activities (IC 50 = 35 and 38 µM, respectively) by targeting both the large and small subunit active sites. (merckmillipore.com)
  • Shown to effectively induce apoptosis (up to 50 µM) in various cancer cell lines (IC 50 ranges from 3.8 to 8.7 µM) in a caspase-3-dependent, but p53-, caspase-8-, and Bak-independent manner. (merckmillipore.com)
  • Results revealed that TL04 treatment improved cell viability and suppressed reactive oxygen species accumulation, lactose dehydrogenase release and caspase-3 activity, and ameliorated mitochondrial abnormal alteration caused by glutamate. (spandidos-publications.com)
  • There are several CLA isomers in ruminant-produced foods, among them c 9, t 11-CLA and t 10, c 12-CLA are more potent against tumor cell growth in vitro [ 2 ]. (biomedcentral.com)
  • However, there is compelling evidence that metacaspases lack caspase activity and that they are not responsible for the caspaselike activities detected during plant and fungal cell death. (rupress.org)
  • Polymorphisms in the CASPASE genes and survival in patients with early-stage non-small-cell lung cancer. (cdc.gov)
  • 10, 11 In such models, aggregate formation and cell death can be reduced by overexpressing yeast and bacteria derived chaperones that do not appear to protect against some other cell death pathways. (bmj.com)
  • Genetic evidence [10, 11] indicates the possible involvement of a FADD-like molecule and caspase-10 rather than of FADD itself and caspase-8. (gale.com)
  • We provide evidence that FADD and caspase-8, but not caspase-10, are recruited to the receptor. (gale.com)
  • The activated receptor transmits the signal to the cytoplasm by recruiting FADD, which forms a death-inducing signalling complex (DISC) with caspase-8. (embl.de)
  • We further suggest that metacaspases and paracaspases, although sharing structural and mechanistic features with the metazoan caspases, form a distinct family of clan CD cysteine peptidases. (rupress.org)
  • Axotomy in vitro leads to a fourfold to sixfold increase in 3 H-leucine incorporation in both neurones and axons, starting within 10 min and peaking 1 h after axotomy. (jneurosci.org)
  • RESULTS: Among the 196 GM taxa, the IVW results confirmed that Family -Peptococcaceae (P = 2.17 × 10-3), Genus- Hungatella (P = 4.57 × 10-3) and genus-Eubacterium_rectale_group (P = 0.02) were correlated with the risk of ON based on Finngen GWAS. (bvsalud.org)
  • The present study aims to assess the gene alterations in the Caspase family of cytochromes so as to derive an association with HNSCC. (who.int)
  • This domain includes the core of p45 (45kDa) precursor of caspases, which can be processed to produce the active p20 (20kDa) and p10 (10kDa) subunits. (embl.de)
  • Exposure to glutamate strongly increased the activity of caspase‑8, caspase‑9 and caspase‑3, which were significantly reversed by TL04 pretreatment. (spandidos-publications.com)
  • In fact, most microglia in the developing CNS are in an activated state as judged top 10 binary option brokers their mor- phology and phagocytic activity. (forextrading-madeeasy.com)
  • Caspases are synthesized as inactive pro-caspases. (smpdb.ca)