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.
Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 7; CASPASE 8; and CASPASE 10. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
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 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.
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 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.
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.
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 long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Activation of this enzyme can occur via the interaction of its caspase recruitment domain with CARD SIGNALING ADAPTOR PROTEINS. Caspase 2 plays a role in APOPTOSIS by cleaving and activating effector pro-caspases. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
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.
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.
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.
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.
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)
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.
A conserved class of proteins that control APOPTOSIS in both VERTEBRATES and INVERTEBRATES. IAP proteins interact with and inhibit CASPASES, and they function as ANTI-APOPTOTIC PROTEINS. The protein class is defined by an approximately 80-amino acid motif called the baculoviral inhibitor of apoptosis repeat.
A long pro-domain caspase that 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 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.
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)
ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
A 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.
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.
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.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
A long pro-domain caspase that contains a death effector domain in its pro-domain region. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS. Caspase 10 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
A 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.
A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.
Peptides composed of between two and twelve amino acids.
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 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.
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.
Physiologically inactive substances that can be converted to active enzymes.
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.
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)
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.
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 3.4.22.4.
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.
Established cell cultures that have the potential to propagate indefinitely.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
A 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 cell line derived from cultured tumor cells.
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 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 protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.
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.
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.
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.
Transport proteins that carry specific substances in the blood or across cell membranes.
The voltage difference, normally maintained at approximately -180mV, across the INNER MITOCHONDRIAL MEMBRANE, by a net movement of positive charge across the membrane. It is a major component of the PROTON MOTIVE FORCE in MITOCHONDRIA used to drive the synthesis of ATP.
The 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.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
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.
Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.
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.
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.
Dried aged bark of a buckthorn, Frangula purshiana (FRANGULA), that contains the anthraquinone EMODIN and cascarosides. It is used as a laxative (CATHARTICS).
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.
Proteins prepared by recombinant DNA technology.
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 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.
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.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
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.
A short pro-domain caspase that is almost exclusively expressed in the EPIDERMIS and may play a role in the differentiation of epidermal KERATINOCYTES.
Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.
The 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.
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.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
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.
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 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.
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 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).
Nuclear matrix proteins that are structural components of the NUCLEAR LAMINA. They are found in most multicellular organisms.
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.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.
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.
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.
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.
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.
Glycoproteins found on the membrane or surface of cells.
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.
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.
Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.
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.
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.
Elements of limited time intervals, contributing to particular results or situations.
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.
Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.
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 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
An inhibitor of SERINE ENDOPEPTIDASES. Acts as an alkylating agent and is known to interfere with the translation process.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
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.
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 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.
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Proteins found in any species of virus.
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.
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 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).
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.
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 of cleaving a chemical compound by the addition of a molecule of water.
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)
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.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.
A 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.

Bcl-2 regulates amplification of caspase activation by cytochrome c. (1/9903)

Caspases, a family of specific proteases, have central roles in apoptosis [1]. Caspase activation in response to diverse apoptotic stimuli involves the relocalisation of cytochrome c from mitochondria to the cytoplasm where it stimulates the proteolytic processing of caspase precursors. Cytochrome c release is controlled by members of the Bcl-2 family of apoptosis regulators [2] [3]. The anti-apoptotic members Bcl-2 and Bcl-xL may also control caspase activation independently of cytochrome c relocalisation or may inhibit a positive feedback mechanism [4] [5] [6] [7]. Here, we investigate the role of Bcl-2 family proteins in the regulation of caspase activation using a model cell-free system. We found that Bcl-2 and Bcl-xL set a threshold in the amount of cytochrome c required to activate caspases, even in soluble extracts lacking mitochondria. Addition of dATP (which stimulates the procaspase-processing factor Apaf-1 [8] [9]) overcame inhibition of caspase activation by Bcl-2, but did not prevent the control of cytochrome c release from mitochondria by Bcl-2. Cytochrome c release was accelerated by active caspase-3 and this positive feedback was negatively regulated by Bcl-2. These results provide evidence for a mechanism to amplify caspase activation that is suppressed at several distinct steps by Bcl-2, even after cytochrome c is released from mitochondria.  (+info)

Caspase-mediated cleavage of p21Waf1/Cip1 converts cancer cells from growth arrest to undergoing apoptosis. (2/9903)

The cyclin-dependent kinase inhibitor p21waf1/Cip1 is a downstream effector of the p53-dependent cell growth arrest. We report herein that p21 was cleaved by caspase-3/CPP32 at the site of DHVD112L during the DNA damage-induced apoptosis of cancer cells. The cleaved p21 fragment could no more arrest the cells in G1 phase nor suppress the cells undergoing apoptosis because it failed to bind to the proliferating cell nuclear antigen (PCNA) and lost its capability to localize in the nucleus. Thus, caspase-3-mediated cleavage and inactivation of p21 protein may convert cancer cells from growth arrest to undergoing apoptosis, leading to the acceleration of chemotherapy-induced apoptotic process in cancer cells.  (+info)

Caspase 3 inactivation to suppress Fas-mediated apoptosis: identification of binding domain with p21 and ILP and inactivation machinery by p21. (3/9903)

The death mediator caspase acts as the dominant regulator during cell death induction. The CPP32 subfamily, including caspase 3 (CPP32/Yama/Apopain), is essential for the cell death signaling. We recently reported that activation of caspase 3 is regulated by complex formation with p21 or ILP. In the present study, we investigated the binding domain with p21 and ILP to further characterize the caspase 3 inactivation machinery. Our results show that caspase 3 contains p21 binding domain in the N-terminus and ILP binding domain in the active site. Further, the caspase 3 binding domain in p21 was independent of the Cdk- or PCNA-binding domain. We also found caspase 3 protection by p21 from the p3-site cleavage serineproteinase contributes to the suppression machinery. Here, we propose the caspase 3 inactivation system by p21 and ILP as new essential system in the regulation of cell death.  (+info)

Activation of c-Abl tyrosine kinase requires caspase activation and is not involved in JNK/SAPK activation during apoptosis of human monocytic leukemia U937 cells. (4/9903)

Genotoxic stress triggers the activation of several sensor molecules, such as p53, JNK1/SAPK and c-Abl, and occasionally promotes the cells to apoptosis. We previously reported that JNK1/SAPK regulates genotoxic stress-induced apoptosis in p53-negative U937 cells by activating caspases. c-Abl is expected to act upstream of JNK1/SAPK activation upon treatment with genotoxic stressors, but its involvement in apoptosis development is still unclear. We herein investigated the kinase activities of c-Abl and JNK1/SAPK during apoptosis elicited by genotoxic anticancer drugs and tumor necrosis factor (TNF) in U937 cells and their apoptosis-resistant variant UK711 cells. We found that the activation of JNK1/SAPK and c-Abl correlated well with apoptosis development in these cell lines. Unexpectedly, however, the JNK1/SAPK activation preceded the c-Abl activation. Moreover, the caspase inhibitor Z-Asp suppressed c-Abl activation and the onset of apoptosis but not the JNK1/SAPK activation. Interestingly, c-Abl tyrosine kinase inhibition by CGP 57148 reduced apoptosis without interfering with JNK1/SAPK activation. These results indicate that c-Abl acts not upstream of JNK1/ SAPK but downstream of caspases during the development of p53-independent apoptosis and is possibly involved in accelerating execution of the cell death pathway.  (+info)

Fas/Apo [apoptosis]-1 and associated proteins in the differentiating cerebral cortex: induction of caspase-dependent cell death and activation of NF-kappaB. (5/9903)

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

Activation of stress-activated protein kinase/c-Jun NH2-terminal kinase and p38 kinase in calphostin C-induced apoptosis requires caspase-3-like proteases but is dispensable for cell death. (6/9903)

Apoptosis was induced in human glioma cell lines by exposure to 100 nM calphostin C, a specific inhibitor of protein kinase C. Calphostin C-induced apoptosis was associated with synchronous down-regulation of Bcl-2 and Bcl-xL as well as activation of caspase-3 but not caspase-1. The exposure to calphostin C led to activation of stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) and p38 kinase and concurrent inhibition of extracellular signal-regulated kinase (ERK). Upstream of ERK, Shc was shown to be activated, but its downstream Raf1 and ERK were inhibited. The pretreatment with acetyl-Tyr-Val-Ala-Asp-aldehyde, a relatively selective inhibitor of caspase-3, or benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD.fmk), a broad spectrum caspase inhibitor, similarly inhibited calphostin C-induced activation of SAPK/JNK and p38 kinase as well as apoptotic nuclear damages (chromatin condensation and DNA fragmentation) and cell shrinkage, suggesting that caspase-3 functions upstream of SAPK/JNK and p38 kinase, but did not block calphostin C-induced surface blebbing and cell death. On the other hand, the inhibition of SAPK/JNK by transfection of dominant negative SAPK/JNK and that of p38 kinase by SB203580 induced similar effects on the calphostin C-induced apoptotic phenotypes and cell death as did z-VAD.fmk and acetyl-Tyr-Val-Ala-Asp-aldehyde, but the calphostin C-induced PARP cleavage was not changed, suggesting that SAPK/JNK and p38 kinase are involved in the DNA fragmentation pathway downstream of caspase-3. The present findings suggest, therefore, that the activation of SAPK/JNK and p38 kinase is dispensable for calphostin C-mediated and z-VAD.fmk-resistant cell death.  (+info)

Proteolytic processing of the Alzheimer's disease amyloid precursor protein within its cytoplasmic domain by caspase-like proteases. (7/9903)

Alzheimer's disease is characterized by neurodegeneration and deposition of betaA4, a peptide that is proteolytically released from the amyloid precursor protein (APP). Missense mutations in the genes coding for APP and for the polytopic membrane proteins presenilin (PS) 1 and PS2 have been linked to familial forms of early-onset Alzheimer's disease. Overexpression of presenilins, especially that of PS2, induces increased susceptibility for apoptosis that is even more pronounced in cells expressing presenilin mutants. Additionally, presenilins themselves are targets for activated caspases in apoptotic cells. When we analyzed APP in COS-7 cells overexpressing PS2, we observed proteolytic processing close to the APP carboxyl terminus. Proteolytic conversion was increased in the presence of PS2-I, which encodes one of the known PS2 pathogenic mutations. The same proteolytic processing occurred in cells treated with chemical inducers of apoptosis, suggesting a participation of activated caspases in the carboxyl-terminal truncation of APP. This was confirmed by showing that specific caspase inhibitors blocked the apoptotic conversion of APP. Sequence analysis of the APP cytosolic domain revealed a consensus motif for group III caspases ((IVL)ExD). Mutation of the corresponding Asp664 residue abolished cleavage, thereby identifying APP as a target molecule for caspase-like proteases in the pathways of programmed cellular death.  (+info)

Role of hypoxia-induced Bax translocation and cytochrome c release in reoxygenation injury. (8/9903)

We investigated mechanisms of cell death during hypoxia/reoxygenation of cultured kidney cells. During glucose-free hypoxia, cell ATP levels declined steeply resulting in the translocation of Bax from cytosol to mitochondria. Concurrently, there was cytochrome c release and caspase activation. Cells that leaked cytochrome c underwent apoptosis after reoxygenation. ATP depletion induced by a mitochondrial uncoupler resulted in similar alterations even in the presence of oxygen. Moreover, inclusion of glucose during hypoxia prevented protein translocations and reoxygenation injury by maintaining intracellular ATP. Thus, ATP depletion, rather than hypoxia per se, was the cause of protein translocations. Overexpression of Bcl-2 prevented cytochrome c release and reoxygenation injury without ameliorating ATP depletion or Bax translocation. On the other hand, caspase inhibitors did not prevent protein translocations, but inhibited apoptosis during reoxygenation. Nevertheless, they could not confer long-term viability, since mitochondria had been damaged. Omission of glucose during reoxygenation resulted in continued failure of ATP production, and cell death with necrotic morphology. In contrast, cells expressing Bcl-2 had functional mitochondria and remained viable during reoxygenation even without glucose. Therefore, Bax translocation during hypoxia is a molecular trigger for cell death during reoxygenation. If ATP is available during reoxygenation, apoptosis develops; otherwise, death occurs by necrosis. By preserving mitochondrial integrity, BCL-2 prevents both forms of cell death and ensures cell viability.  (+info)

Apoptosis is a process of fundamental importance to multicellular organisms that enables control of cell populations and the removal of damaged or potentially harmful cells (Arends and Wyllie 1991). Apoptosis occurs in two phases: an initial commitment phase followed by an execution phase involving cytoskeletal disruption, membrane blebbing, condensation and fragmentation of chromatin, and the formation of apoptotic bodies (Earnshaw 1995). Caspases, a family of aspartate-specific cysteine proteases, play a critical role in the execution phase of apoptosis and are the key effectors responsible for many of the dramatic morphological and biochemical changes of apoptosis (for reviews see Cohen 1997; Thornberry and Lazebnik 1998). Caspases are proteolytically cleaved at specific aspartate residues, generating a large and small subunit that together form the active enzyme. Caspases can be divided into two classes: (1) initiator caspases, with long prodomains, such as caspases-8 and -9, which either ...
Fingerprint Dive into the research topics of Casiopeina III-ia induces apoptosis in HCT-15 cells in vitro through caspase-dependent mechanisms and has antitumor effect in vivo. Together they form a unique fingerprint. ...
We used cytoplasmic extracts from chicken DU249 cells at various stages along the apoptotic pathway to analyse the events of apoptotic exe-cution. So-called S/M extracts from morphologically normal committed-stage cells induce apoptotic morphology and DNA cleavage in substrate nuclei. These apoptotic changes appear to require the function of multiple caspases (cysteine aspar-tases, a specialized class of proteases) acting in parallel. Extracts from execution-stage apoptotic cells induce apoptotic events in added nuclei in a caspase-independent manner. Biochemical frac-tionation of these extracts reveals that a column fraction enriched in endogenous active caspases is un-able to induce DNA fragmentation or chromatin condensation in substrate nuclei, whereas a caspase-depleted fraction induces both changes. Execution-stage extracts contain an ICAD/DFF45-inhibitable nuclease resembling CAD, plus another activity that is required for the apoptotic chromatin condensation. Committed-stage S/M ...
Caspases, aspartate-specific cysteine proteases, have fate-determining roles in many cellular processes including apoptosis, differentiation, neuronal remodeling, and inflammation (for review, see Yuan & Kroemer, 2010). There are a dozen caspases in humans alone, yet their individual contributions toward these phenotypes are not well understood. Thus, there has been considerable interest in activating individual caspases or using their activity to drive these processes in cells and animals. We envision that such experimental control of caspase activity can not only afford novel insights into fundamental biological problems but may also enable new models for disease and suggest possible routes to therapeutic intervention. In particular, localized, genetic, and small-molecule-controlled caspase activation has the potential to target the desired cell type in a tissue. Suppression of caspase activation is one of the hallmarks of cancer and thus there has been significant enthusiasm for generating ...
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA,. All rights reserved. This chapter highlights the prevalence of protein kinase signaling in apoptotic pathways and emphasizes the emergence of global strategies to systematically investigate bidirectional crosstalk between protein kinase phosphorylation and caspase-mediated proteolysis in the propagation of irreversible apoptotic induction. Caspases are classified as cysteine proteases that catalyze irreversible cleavage of peptide bonds C-terminal to aspartic acid residues. The apoptotic role of protein kinases is of interest because posttranslational phosphorylation of both caspases and caspase substrates affects caspase functionality, and conversely, a variety of protein kinases are proteolytically digested by caspases to facilitate or prevent apoptosis. Throughout this chapter, examples have been provided highlighting the complex interactions between protein kinases and caspases that facilitate the progression of apoptosis. The emergence of novel
Caspases are key components of apoptotic pathways. Regulation of caspases occurs at several levels, including transcription, proteolytic processing, inhibition of enzymatic function, and protein degradation. In contrast, little is known about the extent of post-transcriptional control of caspases. Here, we describe four conserved RNA-binding proteins (RBPs)-PUF-8, MEX-3, GLD-1, and CGH-1-that sequentially repress the CED-3 caspase in distinct regions of the Caenorhabditis elegans germline. We demonstrate that GLD-1 represses ced-3 mRNA translation via two binding sites in its 3′ untranslated region (UTR), thereby ensuring a dual control of unwanted cell death: at the level of p53/CEP-1 and at the executioner caspase level. Moreover, we identified seven RBPs that regulate human caspase-3 expression and/or activation, including human PUF-8, GLD-1, and CGH-1 homologs PUM1, QKI, and DDX6. Given the presence of unusually long executioner caspase 3′ UTRs in many metazoans, translational control of ...
Caspases are a conserved family of cysteine proteases. They play diverse roles in inflammatory responses and apoptotic pathways. Among the caspases is a subgroup whose primary function is to initiate apoptosis. Within their long prodomains, caspases-2, -9 and -12 contain a caspase activation and recruitment domain while caspases-8 and -10 bear death effector domains. Activation follows the recruitment of the procaspase molecule via the prodomain to a high molecular mass complex. Despite sharing some common features, other aspects of the biochemistry, substrate specificity, regulation and signaling mechanisms differ between initiator apoptotic caspases. Defects in expression or activity of these caspases are related to certain pathological conditions including neurodegenerative disorders, autoimmune diseases and cancer ...
Follicle cells undergo premature caspase-dependent cell death in lrrk NS flies. (A) Schematic depicting a stage-12 egg chamber, with anterior to the left and po
In previous study we showed that caspase-2 plays the role of an apical caspase in cell death induction by taxanes in breast cancer cells. This study deals with the role of other caspases. We tested breast cancer cell lines SK-BR-3 (functional caspase-3) and MCF-7 (nonfunctional caspase-3). Using western blot analysis we demonstrated the activation of initiator caspase-8 and -9 as well as executioner caspase-6 and -7 in both tested cell lines after application of taxanes (paclitaxel, SB-T-1216) at death-inducing concentrations. Caspase-3 activation was also found in SK-BR-3 cells. Employing specific siRNAs after taxane application, suppression of caspase-3 expression significantly increased the number of surviving SK-BR-3 cells. Inhibition of caspase-7 expression also increased the number of surviving SK-BR-3 and MCF-7 cells. On the other hand, suppression of caspase-8 and caspase-9 expression had no significant effect on cell survival. However, caspase-9 seemed to be involved in the activation of
Apoptosis is a major form of cell death, characterized initially by a series of stereotypic morphological changes. In the nematode Caenorhabditis elegans, the gene ced-3 encodes a protein required for developmental cell death. Since the recognition that CED-3 has sequence identity with the mammalian cysteine protease interleukin-1β-converting enzyme (ICE), a family of at least 10 related cysteine proteases has been identified. These proteins are characterized by almost absolute specificity for aspartic acid in the P1 position. All the caspases (ICE-like proteases) contain a conserved QACXG (where X is R, Q or G) pentapeptide active-site motif. Caspases are synthesized as inactive proenzymes comprising an N-terminal peptide (prodomain) together with one large and one small subunit. The crystal structures of both caspase-1 and caspase-3 show that the active enzyme is a heterotetramer, containing two small and two large subunits. Activation of caspases during apoptosis results in the cleavage of ...
Generic Caspase Activity Assay Kit (Fluorometric - Green) (ab112130). Detect generic caspase activation in live cells with green TF2-VAD-FMK substrate.
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Pyroptosis is a unique, pro‐inflammatory form of lytic cell death that is initiated by the activation of inflammatory caspases. The caspase substrate gasdermin D (GSDMD) plays a critical function in pyroptosis, yet the precise mode of action of this molecule in cell death execution remained unclear. Several recent reports, including a The EMBO Journal article, show that the caspase‐matured N‐terminal fragment of GSDMD is recruited to lipid membranes to form pore‐like structures, which constitutes the key effector mechanism of pyroptotic cell death.. See also: L Sborgi et al (August 2016) ...
Apoptosis or programmed death is a physiological process responsible for normal development and homeostasis of multicellular organisms. This process involves a well-functioning machinery of death, which are the main component of cysteine ​​proteases - caspases family. These enzymes are present in cells in a latent form and become activated during apoptosis induced by various factors. This review summarizes the progress made on structure, mechanism of activation, catalytic properties, are substrates of caspases and regulation of their activity. Also shown in the involvement of caspases in the major pathways of apoptosis.. ...
Detail záznamu - Role of Caspases and CD95/Fas in the Apoptotic Effects of a Nucleotide Analog PMEG in CCRF-CEM Cells - Detail záznamu - Knihovna Akademie věd České republiky
Apoptosis, the most abundant form of programmed cell death during metazoan development, is executed by proteases called caspases. Efforts of many research groups have led to a deep understanding of how caspases are activated and regulated during apoptotic cell death. However, a constantly growing body of research has uncovered new caspase-dependent non-lethal cellular processes (CDPs), of which the molecular regulatory and executional mechanisms are much less understood. CDPs have been reported to modulate many basic cellular processes, such as signaling, proliferation, differentiation, remodeling and neuronal plasticity in a large variety of cell types and organisms. Unsurprisingly, this functional diversity of CDPs might trigger and sustain a wide range of diseases, including cancer and neurodegenerative disorders. Furthermore, it is perceived that caspase-regulating molecules could be a promising avenue for developing new therapeutic strategies. Given the recent explosion of reports and the ...
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 which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein can undergo autoproteolytic processing and activation by the apoptosome, a protein complex of cytochrome c and the apoptotic peptidase activating factor 1; this step is thought to be one of the earliest in the caspase activation cascade. This protein is thought to play a central role in apoptosis and to be a tumor suppressor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013 ...
Downstream activation of caspases and enhanced phosphatidylserine (PS) exposure after long-term blockage of NMDAR in differentiating EPCs. EPCs obtained from th
The Proteasome-Glo™ Cell-Based Assays are homogeneous, luminescent assays that measure the chymotrypsin-like, trypsin-like and caspase-like protease activities associated with the proteasome complex in cultured cells.
I am curious about something. People with CFS have been shown to have higher than normal levels of apoptosis (programmed cell death). According to...
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.
First, the up to date Ensembl IDs have been retrieved for the many genes with SD three between rapamycin and Ly294002 therapies. The Amuvatinib 溶解度 GO lessons
TY - JOUR. T1 - Cloning and expression of rat caspase-6 and its localization in renal ischemia/reperfusion injury. AU - Singh, Amar B.. AU - Kaushal, Varsha. AU - Megyesi, Judit K.. AU - Shah, Sudhir V.. AU - Kaushal, Gur P.. PY - 2002/1/1. Y1 - 2002/1/1. N2 - Background. Caspase-6 is an important member of the executioner caspases in the caspase family of cell death proteases. The executioner caspases are the major active caspases detected in apoptotic cells and are generally considered to mediate the execution of apoptosis by cleaving and inactivating intracellular proteins. However, the complete characterization of mRNA and protein of caspase-6 in rat and its expression in normal kidney and in disease state has not been previously elucidated. Methods. A rat kidney cortex λgt10 cDNA library was screened to isolate the full-length caspase-6 cDNA. The recombinant caspase-6 protein was characterized by expression in bacteria and by transient transfection in mammalian cells. The expression in ...
Psoriasis is a chronic autoimmune disorder of the skin. In this disease, the inflammatory caspases, cysteine proteases involved in the processing of many proteins, are activated. Transgenic mice expressing the cleaved form of caspases by Lyn, a tyrosine kinase Src family, develop an inflammatory syndrome with the characteristics of human psoriasis.. To clarify the relationship between the cleaved form of Lyn by caspases and psoriasis, the investigators intend to develop a clinical study to analyze the expression, cleavage and activity of Lyn and the activation of caspases from skin biopsies of patients with this disease.. This study will be conducted on a cohort of patients with different forms of psoriasis (plaque, pustular and erythrodermic) and atopic dermatitis, another skin disorder associated with chronic inflammation. Thus, the investigators will evaluate the expression and activity of Lyn from skin lesion (L) and non-lesional (NL) from the same patient in parallel with the level of ...
1. WelchmanRLGordonCMayerRJ 2005 Ubiquitin and ubiquitin-like proteins as multifunctional signals. Nat Rev Mol Cell Biol 6 599 609. 2. HickeLSchubertHLHillCP 2005 Ubiquitin-binding domains. Nat Rev Mol Cell Biol 6 610 621. 3. ChenZJSunLJ 2009 Nonproteolytic functions of ubiquitin in cell signaling. Mol Cell 33 275 286. 4. MukhopadhyayDRiezmanH 2007 Proteasome-independent functions of ubiquitin in endocytosis and signaling. Science 315 201 205. 5. LeeTVDingTChenZRajendranVScherrH 2008 The E1 ubiquitin-activating enzyme Uba1 in Drosophila controls apoptosis autonomously and tissue growth non-autonomously. Development 135 43 52. 6. DegterevAYuanJ 2008 Expansion and evolution of cell death programmes. Nat Rev Mol Cell Biol 9 378 390. 7. KumarS 2007 Caspase function in programmed cell death. Cell Death Differ 14 32 43. 8. BaoQShiY 2007 Apoptosome: a platform for the activation of initiator caspases. Cell Death Differ 14 56 65. 9. RiedlSJSalvesenGS 2007 The apoptosome: signalling platform of cell ...
The initiating events that lead to the induction of apoptosis mediated by the chemopreventative agent β-phenyethyl isothiocyanate (PEITC) have yet to be elucidated. In the present investigation, we examined the effects of PEITC on mitochondrial function and apoptotic signaling in hepatoma HepG2 cells and isolated rat hepatocyte mitochondria. PEITC induced a conformational change in Bax leading to its translocation to mitochondria in HepG2 cells. Bax accumulation was associated with a rapid loss of mitochondrial membrane potential (Δψm), impaired respiratory chain enzymatic activity, release of mitochondrial cytochrome c and the activation of caspase-dependent cell death. Caspase inhibition did not prevent Bax translocation, the release of cytochrome c or the loss of Δψ m, but blocked caspase-mediated DNA fragmentation and cell death. To determine whether PEITC dependent Bax translocation caused loss of Δψm by the activation of the mitochondrial permeability transition (MPT), we examined ...
Caspase 12 is a protein that belongs to a family of enzymes called caspases which cleave their substrates at C-terminal aspartic acid residues. It is closely related to caspase 1 and other members of the caspase family, known as inflammatory caspases, which process and activate inflammatory cytokines such as interleukin 1 and interleukin 18. It is found on chromosome 11 in humans in a locus with other inflammatory caspases. CASP12 orthologs have been identified in numerous mammals for which complete genome data are available. The CASP12 gene is subject to polymorphism, which can generate a full length caspase protein (Csp12L) or an inactive truncated form (Csp12S). The functional form appears to be confined to people of African descent and is linked with susceptibility to sepsis; people carrying the functional gene have decreased responses to bacterial molecules such as lipopolysaccharide (LPS). A study in May 2009 by McGill University Health Centre has suggested that estrogen may serve to block ...
The mammalian Golgi complex is comprised of a ribbon of stacked cisternal membranes often located in the pericentriolar region of the cell. Here, we report that during apoptosis the Golgi ribbon is fragmented into dispersed clusters of tubulo-vesicular membranes. We have found that fragmentation is caspase dependent and identified GRASP65 (Golgi reassembly and stacking protein of 65 kD) as a novel caspase substrate. GRASP65 is cleaved specifically by caspase-3 at conserved sites in its membrane distal COOH terminus at an early stage of the execution phase. Expression of a caspase-resistant form of GRASP65 partially preserved cisternal stacking and inhibited breakdown of the Golgi ribbon in apoptotic cells. Our results suggest that GRASP65 is an important structural component required for maintenance of Golgi apparatus integrity.
The caspase-3 (CPP32, apopain, YAMA) family of cysteinyl proteases has been implicated as key mediators of apoptosis in mammalian cells. Gelsolin was identified as a substrate for caspase-3 by screening the translation products of small complementary DNA pools for sensitivity to cleavage by caspase-3. Gelsolin was cleaved in vivo in a caspase-dependent manner in cells stimulated by Fas. Caspase-cleaved gelsolin severed actin filaments in vitro in a Ca2+-independent manner. Expression of the gelsolin cleavage product in multiple cell types caused the cells to round up, detach from the plate, and undergo nuclear fragmentation. Neutrophils isolated from mice lacking gelsolin had delayed onset of both blebbing and DNA fragmentation, following apoptosis induction, compared with wild-type neutrophils. Thus, cleaved gelsolin may be one physiological effector of morphologic change during apoptosis. ...
Death receptor (DR) ligation can lead to divergent signaling pathways causing either caspase-mediated cell death or cell proliferation and inflammation. These variations in cellular fate are determined by adaptor proteins that are recruited to the DR signaling complex. FLICE inhibitory protein (FLIP) is an established inhibitor of caspase-8-mediated apoptosis, and it is also involved in NF-kappa B
Zeng L., Li T., Xu D.C., Liu J., Mao G., Cui M.Z., Fu X., Xu X.. Cells undergo apoptosis through two major pathways, the extrinsic pathway (death receptor pathway) and the intrinsic pathway (the mitochondrial pathway). These two pathways can be linked by caspase-8-activated truncated Bid formation. Very recently, death receptor 6 (DR6) was shown to be involved in the neurodegeneration observed in Alzheimer disease. DR6, also known as TNFRSF21, is a relatively new member of the death receptor family, and it was found that DR6 induces apoptosis when it is overexpressed. However, how the death signal mediated by DR6 is transduced intracellularly is not known. To this end, we have examined the roles of caspases, apoptogenic mitochondrial factor cytochrome c, and the Bcl-2 family proteins in DR6-induced apoptosis. Our data demonstrated that Bax translocation is absolutely required for DR6-induced apoptosis. On the other hand, inhibition of caspase-8 and knockdown of Bid have no effect on DR6-induced ...
Apoptosis is a genetically programmed process for the elimination of damaged or redundant cells by activation of caspases (aspartate-specific cysteine proteases). The onset of apoptosis is controlled by numerous interrelating processes. The extrinsic pathway involves stimulation of members of the tumor necrosis factor (TNF) receptor subfamily, such as TNFRI, CD95/Fas or TRAILR (death receptors), located at the cell surface, by their specific ligands, such as TNF-alpha, FasL or TRAIL, respectively. The intrinsic pathway is activated mainly by non-receptor stimuli, such as DNA damage, ER stress, metabolic stress, UV radiation or growth-factor deprivation. The central event in the intrinsic pathway is the mitochondrial outer membrane permeabilization (MOMP), which leads to the release of cytochrome c. These two pathways converge at the level of effector caspases, such as caspase-3 and caspase-7. The third major pathway is initiated by the constituents of cytotoxic granules (e.g. Perforin and ...
Apoptosis is a genetically programmed process for the elimination of damaged or redundant cells by activation of caspases (aspartate-specific cysteine proteases). The onset of apoptosis is controlled by numerous interrelating processes. The extrinsic pathway involves stimulation of members of the tumor necrosis factor (TNF) receptor subfamily, such as TNFRI, CD95/Fas or TRAILR (death receptors), located at the cell surface, by their specific ligands, such as TNF-alpha, FasL or TRAIL, respectively. The intrinsic pathway is activated mainly by non-receptor stimuli, such as DNA damage, ER stress, metabolic stress, UV radiation or growth-factor deprivation. The central event in the intrinsic pathway is the mitochondrial outer membrane permeabilization (MOMP), which leads to the release of cytochrome c. These two pathways converge at the level of effector caspases, such as caspase-3 and caspase-7. The third major pathway is initiated by the constituents of cytotoxic granules (e.g. Perforin and ...
Apoptosis is a genetically programmed process for the elimination of damaged or redundant cells by activation of caspases (aspartate-specific cysteine proteases). The onset of apoptosis is controlled by numerous interrelating processes. The extrinsic pathway involves stimulation of members of the tumor necrosis factor (TNF) receptor subfamily, such as TNFRI, CD95/Fas or TRAILR (death receptors), located at the cell surface, by their specific ligands, such as TNF-alpha, FasL or TRAIL, respectively. The intrinsic pathway is activated mainly by non-receptor stimuli, such as DNA damage, ER stress, metabolic stress, UV radiation or growth-factor deprivation. The central event in the intrinsic pathway is the mitochondrial outer membrane permeabilization (MOMP), which leads to the release of cytochrome c. These two pathways converge at the level of effector caspases, such as caspase-3 and caspase-7. The third major pathway is initiated by the constituents of cytotoxic granules (e.g. Perforin and ...
Mon laboratoire sintéresse aux mécanismes dactivation, de régulation et dactivité des caspases, des enzymes importantes pour une multitude de processus biologiques et pathologiques. À long terme, notre objectif est délucider leur biologie afin de proposer des approches thérapeutiques nouvelles. Les caspases sont des enzymes très importantes pour linflammation, la mort cellulaire et plusieurs autres fonctions incluant diverses pathologies. Par exemple, certaines caspases ont une importance majeure dans les maladies neurodégénératives tel le Parkinson. Un des membres de cette famille, la caspase-7, joue un rôle lors de la mort cellulaire et durant un processus inflammatoire nouveau. Ce processus est important pour la destruction de certains pathogènes. Par conséquent, mon laboratoire sintéresse aux activateurs de la caspase-7, comment elle est contrôlée et comment elle agit sur ses cibles. De cette façon, notre laboratoire étudie plusieurs aspects de la biologie des ...
The robust and rapid induction of innate immune signaling is a hallmark of the host response to microbial infection. Successful pathogens subvert, thwart, or dismantle these defensive measures. Growing evidence suggests that the host recognizes these disruptive efforts, eliciting effective backup measures. Cell death processes, including apoptosis and pyroptosis, are integral components of the host response to infection. Multiprotein inflammasome complexes sense the presence of pathogens and activate inflammatory caspases, typically caspase-1 or caspase-11, leading to pyroptotic cell death and maturation of the inflammatory cytokines interleukin-1β (IL-1β) and IL-18. Pyroptosis is an inflammasome-driven cytotoxic process that occurs in macrophages after limited proteolysis of gasdermin D (GSDMD). The generation of an N-terminally cleaved fragment then creates large oligomeric membrane pores and causes lytic cell death (1-7). At present, caspase-1 and caspase-11 are the only known regulators of ...
This group of sequences represent the core of p45 (45 kDa) precursor of caspases, which can be processed to produce the active p20 (20 kDa) and p10 (10 kDa) subunits. Caspases (Cysteine-dependent ASPartyl-specific proteASE) are cysteine peptidases that belong to the MEROPS peptidase family C14 (caspase family, clan CD) based on the architecture of their catalytic dyad or triad [(PUBMED:11517925)]. Caspases are tightly regulated proteins that require zymogen activation to become active, and once active can be regulated by caspase inhibitors. 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. The catalytic cysteine and histidine residues are on the p20 subunit after cleavage of the p45 precursor.. Caspases are mainly involved in mediating cell death (apoptosis) [(PUBMED:10578171), (PUBMED:10872455), (PUBMED:15077141)]. They have two main roles within the apoptosis cascade: ...
TY - JOUR. T1 - Reversibility of apoptosis in cancer cells. AU - Tang, H. L.. AU - Yuen, K. L.. AU - Tang, H. M.. AU - Fung, M. C.. PY - 2009/1/13. Y1 - 2009/1/13. N2 - Apoptosis is a cell suicide programme characterised by unique cellular events such as mitochondrial fragmentation and dysfunction, nuclear condensation, cytoplasmic shrinkage and activation of apoptotic protease caspases, and these serve as the noticeable apoptotic markers for the commitment of cell demise. Here, we show that, however, the characterised apoptotic dying cancer cells can regain their normal morphology and proliferate after removal of apoptotic inducers. In addition, we demonstrate that reversibility of apoptosis occurs in various cancer cell lines, and in different apoptotic stimuli. Our findings show that cancer cells can survive after initiation of apoptosis, thereby revealing an unexpected potential escape mechanism of cancer cells from chemotherapy.. AB - Apoptosis is a cell suicide programme characterised by ...
When cells kill themselves, they usually do so by activating mechanisms that have evolved specifically for that purpose. These mechanisms, which are broadly conserved throughout the metazoa, involve two processes: activation in the cytosol of latent cysteine proteases (termed caspases), and disruption of mitochondrial functions. These processes are linked in a number of different ways. While active caspases can cleave proteins in the mitochondrial outer membrane, and cleave and thereby activate certain pro-apoptotic members of the Bcl-2 family, proteins released from the mitochondria can trigger caspase activation and antagonise IAP family proteins. This review will focus on the pro-apoptotic molecules that are released from the mitochondria of cells endeavouring to kill themselves. This article is part of a Special Issue entitled Mitochondria: the deadly organelle ...
When cells are infected, pathogen-derived proteins are processed by the proteasome, and the resultant peptides (after further processing) bind to the class I major histocompatibility complex (MHC) and are presented on the surface of the infected cell. CD8+ cytotoxic T lymphocytes (CTLs) recognize these peptide-MHC complexes and kill the infected cell. Noting that viral infection often activates caspases, cytosolic cysteine proteases that trigger apoptosis, López et al. investigated whether caspases might also contribute to antigen presentation. The authors infected murine cells with recombinant vaccinia virus (rVACV) that expressed a miniprotein (m19) and cultured the cells with CTL lines specific for an epitope within m19. The CTLs killed the infected cells and also killed infected cells that were incubated with either a proteasome-specific inhibitor or a caspase-specific inhibitor; however, treatment of the infected cells with both inhibitors blocked killing by the CTLs. Analysis of peptide ...
Caspases are normally suppressed by IAP (inhibitor of apoptosis) proteins (see Controlling the Caspases, by Stephen W. Fesik and Yigong Shi, in Science, Vol. 294, No. 5546, p. 1477, November 16, 2001). When a cell receives an apoptotic stimulus, IAP activity is relieved after SMAC (Second Mitochondria-derived Activator of Caspases, or its mouse homolog, called DIABLO), a mitochondrial protein, is reléased into the cytosol. SMAC binds to IAPs, and in doing so inhibits the inhibitors, effectively preventing them from arresting the apoptotic process. But before we go on to a short description of how SMAC is reléased, lets take a look at two well-studied extrinsically induced apoptotic processes: the TNF and the Fas pathways. Keep in mind, however, that both activating and inhibiting factors are present at éach step of these pathways. Tumor necrosis factor (TNF), a 157 amino acid inter-cellular signaling molecule (cytokine) produced mainly by activated macrophages, and is the major extrinsic ...
TY - JOUR. T1 - Caspases determine the vulnerability of oligodendrocytes in the ischemic brain. AU - Shibata, Mamoru. AU - Hisahara, Shin. AU - Hara, Hideaki. AU - Yamawaki, Takemori. AU - Fukuuchi, Yasuo. AU - Yuan, Junying. AU - Okano, Hideyuki. AU - Miura, Masayuki. PY - 2000/9. Y1 - 2000/9. N2 - Although oligodendrocytes (OLGs) are thought to be vulnerable to hypoxia and ischemia, little is known about the detailed mechanism by which these insults induce OLG death. From the clinical viewpoint, it is imperative to protect OLGs as well as neurons against ischemic injury (stroke), because they are the only myelin-forming cells of the central nervous system. Using the Cre/loxP system, we have established a transgenic mouse line that selectively expresses p35, a broad-spectrum caspase inhibitor, in OLGs. After hypoxia, cultured OLGs derived from wild-type mice exhibited significant upregulation of caspase-11 and substantial activation of caspase-3, which led to cell loss. Expression of p35 or ...
The present study examined levels of various components of the cell death machinery and drug sensitivity of 60 human cancer cell lines to anticancer drugs. With the exception of procaspase-3, which was undetectable in MCF-7 cells, caspases-2, -3, -6, -7, -8, and -9, as well as Apaf-1, were detectable in all 60 cell lines. Although these components of the cell death machinery varied widely in abundance, strong correlations between levels of Apaf-1 or procaspase-2, -3, -6, -8, or -9 and sensitivity to any class of antineoplastic agent were not observed. These results, although negative, have several important implications.. The attempt to correlate drug sensitivity with levels of various components of the cell death machinery was prompted by previous studies indicating that drug-induced apoptosis is markedly diminished when certain key components of the core cell-death machinery, particularly Apaf-1, procaspase-9, or procaspase-3, are genetically or functionally deleted (36, 37, 38 , 58 , 88 , 99) ...
Caspase-3 is a caspase protein that interacts with caspase-8 and caspase-9. It is encoded by the CASP3 gene. CASP3 orthologs have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts. The CASP3 protein 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 6 and 7; and the protein itself is processed and activated by caspases 8, 9, and 10. It is the predominant caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is associated with neuronal death in Alzheimers disease. Alternative splicing of this gene results in two ...
PTK787 2HCl and -7 (Lakhani et al. 2006 offers contributed to your knowledge of the physiological tasks of the caspases significantly. Oddly enough C57BL/6 mice deficient for both caspase-3 and -7 perish shortly after delivery while mice missing only caspase-3 or -7 have a normal life span and display a limited apoptotic phenotype in this genetic background (Lakhani et al. 2006 Leonard et al. 2002 This points to the functional redundancy between caspase-3 and -7 during embryogenesis. However several observations suggest that this overlap is not complete and that caspase-3 and -7 also fulfill non-redundant roles in apoptosis. For instance eye lenses of caspase-7 knockout mice are grossly normal whereas those of caspase-3 deficient mice display marked cataracts at the anterior lens pole (Zandy et al. 2005 Further support for this notion stems from biochemical studies demonstrating that caspase-3 and -7 exhibit differential activities toward multiple protein substrates with caspase-7 being more ...
Materials.Benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk), z-Asp-Glu-Val-Asp-fmk (zDEVD-fmk), boc-aspartyl(OMe)-fluoromethylketone (BAF), and the fluorogenic caspase substrate zDEVD-AFC were purchased from Enzyme Systems Products (Livermore, CA). Staurosporine was obtained from ICN Pharmaceuticals (Costa Mesa, CA). A cell lysis buffer for fluorogenic caspase activity assays was obtained from Clontech (ApoAlert CPP32 Assay Kit; Palo Alto, CA).. Cell culture. p53-deficient mice were generated from a 129/Sv × C57BL/6 background as described (Donehower et al., 1992). The genotypes of the mating pairs and all offspring were determined by PCR, using DNA extracted from the tail (Timme and Thompson, 1994). p53−/− mice were generated routinely from (+/−) × (−/−) mating pairs, whereas p53 wild-type mice were obtained by crossing p53+/+ mice. The brains from individual animals were cultured separately and genotyped before treatment.. Neuronal cultures derived from embryonic day ...
Caspases are important players in programmed cell death. Normal activities of caspases are critical for the cell life cycle and dysfunction of caspases may lead to the development of cancer and neurodegenerative diseases. They have become a popular target for drug design against abnormal cell death. In this study, the recognition of P5 position in substrates by caspase-3, -6 and -7 has been investigated by kinetics, modeling and crystallography. Crystal structures of caspase-3 and -7 in complexes with substrate analog inhibitor Ac-LDESD-CHO have been determined at resolutions of 1.61 and 2.45 Å, respectively, while a model of caspase-6/LDESD is constructed. Enzymatic study and structural analysis have revealed that Caspase-3 and -6 recognize P5 in pentapeptides, while caspase-7 lacks P5-binding residues. D-arginine dehydrogenase catalyzes the flavin-dependent oxidative deamination of D-amino acids to the corresponding imino acids and ammonia. The X-ray crystal structures of DADH and its complexes with
BioAssay record AID 666968 submitted by ChEMBL: Inhibition of human recombinant caspase-3 catalytic domain using Ac-DEVD-pNA as substrate at 20 ug/ml preincubated for 30 mins before substrate addition measured after 3 mins.
Caspase-1, originally called ICE, was the first mammalian analogue of the Caenorhabditis elegans death genes to be identified.11 Like all caspases, it is expressed as a proform, which is activated through proteolytic cleavage of an amino-terminal 11-kDa prodomain to release p20 and p10 subunits. Active caspase-1/ICE consists of a (p20/p10)2 tetramer, which is sufficient to process precursor IL-1β9,12-14 and, in at least some cell types, to induce apoptosis.16 Additionally, the prodomain has been postulated to have independent proapoptotic activity by enhancing death receptor-mediated caspase-8 activation.39 Although caspase-1 has conventionally been regarded as a proinflammatory, not a proapoptotic, caspase,10-12 it has been observed to induce or amplify apoptosis in tissue culture models.15,16. Regulated expression of caspase-1 in cardiac hypertrophy,17 the dilated cardiomyopathy of TNF-α overexpression,19 ischemia/infarction,21 and endotoxin-induced myocardial dysfunction18 prompted our ...
The mode of cell death during galactosamine (Gal)-induced liver injury was originally thought to be oncotic necrosis but recently it was suggested to be apoptosis. Thus, the objective was to assess whether apoptosis and oncosis are sequential or independent events in the pathophysiology. In addition, the role of caspases in Gal-induced apoptotic signaling was investigated. A dose of 500 mg/kg Gal caused a time-dependent increase in plasma alanine transaminase (ALT) levels (24 h: 430 ± 122 U/L) in female Sprague-Dawley rats. This was accompanied by processing of procaspase-3 and significant increases in hepatic and plasma caspase-3 activities. Using morphology and TUNEL staining, apoptotic and oncotic cells were quantitated. The number of apoptotic hepatocytes increased from 0.14% in controls to 5.4 ± 1.0% 24 h after Gal treatment. In addition, the number of cells with oncotic morphology increased from 0 to 6.9% of total hepatocytes. Treatment with the pan-caspase inhibitor IDN-7314 (10 mg/kg) or
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MALT1 reglerar medfödd immunitet men hur detta sker är fortfarande oklara. Vi använde den selektiva MALT1 paracaspase hämmaren MLT-827...
The activation of microglia, resident immune cells of the central nervous system, and inflammation-mediated neurotoxicity are typical features of neurodegenerative diseases, for example, Alzheimers and Parkinsons diseases. An unexpected role of caspase-3, commonly known to have executioner role for apoptosis, was uncovered in the microglia activation process. A central question emerging from this finding is what prevents caspase-3 during the microglia activation from killing those cells? Caspase-3 activation occurs as a two-step process, where the zymogen is first cleaved by upstream caspases, such as caspase-8, to form intermediate, yet still active, p19/p12 complex; thereafter, autocatalytic processing generates the fully mature p17/p12 form of the enzyme. Here, we show that the induction of cellular inhibitor of apoptosis protein 2 (cIAP2) expression upon microglia activation prevents the conversion of caspase-3 p19 subunit to p17 subunit and is responsible for restraining caspase-3 in ...
This study investigated the possible involvement of a specific caspase(s) (a family of aspartate-specific cysteine proteases) in programmed cell death of islet beta-cells due to sustained GTP depletion. Treatment (up to 48 h) with 3 microg/ml mycophenolic acid (MPA), which specifically depletes intr …
Commentary 2801 Introduction Apoptosis is essential for normal development and tissue homeostasis, and perturbations in its regulation contribute to numerous pathological conditions, including cancer and autoimmune and degenerative diseases (Adams and Cory, 2007; Meier and Vousden, 2007). There are two main pathways that lead to apoptosis: the extrinsic pathway, which is triggered following the activation of cell-surface-expressed death receptors such as CD95 (also known as Fas receptor) and tumour necrosis factor receptor; and the intrinsic pathway, which is activated by cellular stress and is regulated primarily at the level of mitochondria by the Bcl-2 family of proteins (Fig. 1). The intrinsic apoptotic pathway is initiated in response to a variety of stress signals (Willis and Adams, 2005), and a complex interplay of Bcl-2 proteins relays this signal to the mitochondrial outer membrane (OM) to initiate Bak and Bax activation, oligomerisation and OM damage (Fig. 1). Breaching the ...
Actually, that is a very long story; we worked on that one for some time. We started working on it because of our interest in TNF. Certain cells, when treated with TNF, undergo necrotic cell death. The molecular basis of necrosis is poorly defined right now, but the most practical definition for our study is that it is a form of cell death that, unlike apoptosis, does not involve caspases. We wanted to see if we could find a key molecule that is important for necrosis.. We had been working on this problem for a while when I heard about a paper that another group had published, which claimed that TNF-treated NIH-3T3 cells didnt undergo apoptotic cell death, because if you blocked caspases, the cells would still die. I thought this was interesting because, generally speaking and also in our hands, TNF treatment of NIH-3T3 cells causes apoptosis, and does involve caspases. So we got some of these necrotic NIH-3T3 cells, and we compared their gene expression profile to our apoptotic NIH-3T3 cell ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
The NucView® caspase-3 substrates are activity-dependent i.e. require active caspase-3 enzyme. In dead, fixed and preserved cells or tissue sections, there are no active caspases and hence these substrates cannot be used. We also offer TUNEL assay kits that are suitable for apoptosis detection in fixed cells and tissues. The kits employ dUTPs conjugated to our exceptionally bright and photostable CF® dyes for single-step fluorescent TUNEL labeling of DNA strand breaks, a hallmark of apoptotic cells, and are suitable for analysis by fluorescence microscopy or flow cytometry.. ...
The response of psoriasis to antibodies targeting the interleukin (IL)-23/IL-17A pathway suggests a prominent role of T-helper type-17 (Th17) cells in this disease. had not been detectable in neutrophils isolated from VX-950 dynamic plaques. Significant medical reactions to secukinumab had been noticed 2?weeks following a solitary infusion, connected with extensive clearance of cutaneous neutrophils parallel towards the normalization of keratinocyte abnormalities and reduced amount of IL-17-inducible neutrophil chemoattractants (e.g. (TNF-(monoclonal antibody selective for IL-17A, or placebo inside a 3:3:3:1 percentage (information regarding test size computation, randomization and blinding are given within the Assisting Information). There have been low- and middle- single-dose cohorts who received secukinumab 3 and 10?mg/kg, respectively, infused on Day time 1 (with placebo administered on Day time 15 and Day time 29) along with a high-dose cohort who have received 3 infusions of secukinumab ...
Supplementary MaterialsDataSheet_1. the additional four baseline strategies. Furthermore, we validated the predictions from the MDADTI in six drug-target connections reference databases, as well as the outcomes demonstrated that MDADTI can identify unknown DTIs effectively. = 1,……,? and a couple of goals T?= = 1,……,, where represents the real variety of medications and represents the amount of goals. We also described the connections between D and T being a binary matrix Y whose component beliefs are 0 or 1, where = 1 represents the medication and similarity matrices of goals in = to get the topology framework feature of medication nodes. The RWR strategy can be developed as the next recurrence relationship: is normally a row vector of medication and its techniques starting from 99011-02-6 medication may be the preliminary one-hot vector, is the probability of restart, and is the one-step probability transition matrix acquired by applying row-wise normalization of the similarity matrix ...
In Figure 3, they added the DRACOs to these cells, either with, or without the inhibitor. They also included a product which makes cells which have just self destructed glow in the dark. The first four sections on the graph are simply controls, to pick up the background levels of cell death. Since the main function of caspases is to cause cell death to occur, you can guess what would happen if we were to add caspase inhibitors to a normal set of cells. The blue and red bars are both lower than the green bar , because they have the caspase inhibitors added. The next three sections show what happens when DRACOs are added to the mix, and they show that they kill off a lot of cells. And importantly, you can tell that its performed using caspases, because in the presence of inhibitor, the cells do not die as much. In fact, the levels of death seen is more or less the same as the other controls with inhibitors ...
Apoptosis is a distinct form of cell death that is functionally and morphologically different from necrosis. Nuclear chromatin condensation, cytoplasmic shrinking, dilated endoplasmic reticulum, and membrane blebbing characterize apoptosis in general. Mitochondria remain morphologically unchanged. In 1972 Kerr et al introduced the concept of apoptosis as a distinct form of cell-death, and the mechanisms of various apoptotic pathways are still being revealed today ...
Apoptosis is a distinct form of cell death that is functionally and morphologically different from necrosis. Nuclear chromatin condensation, cytoplasmic shrinking, dilated endoplasmic reticulum, and membrane blebbing characterize apoptosis in general. Mitochondria remain morphologically unchanged. In 1972 Kerr et al introduced the concept of apoptosis as a distinct form of cell-death, and the mechanisms of various apoptotic pathways are still being revealed today ...
In Situ Pan-Caspase Assay Kit from CHEMICON,Apoptosis is an evolutionarily conserved form of cell suicide, which follows a specialized cellular process. The central component of this process is a cascade of proteolytic enzymes called caspases. These enzymes participate in a series of reactions that are triggered in response to pro-apoptoti,biological,biology supply,biology supplies,biology product
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
General characteristics of apoptosis and mechanisms leading to activation of caspases and endonucleases, the main executors of apoptosis is described. The crucial role in these processes of mitochondria and the proteins released from them procaspase 9, cytochrom c and AIF factor is also shown. Information is also presented about membrane receptors, their ligands as well as various regulatory proteins, those from BCL-2/BAX and IAPs families included. It is pointed out that changes in the level of expression and/or properties of regulatory proteins characterize various tumor cells. ...
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There are two types of caspases: initiator caspases, caspase 2,8,9,10,11,12, and effector caspases, caspase 3,6,7. The ... caspase-8 and caspase-10. In some types of cells (type I), processed caspase-8 directly activates other members of the caspase ... The apoptosome cleaves the pro-caspase to its active form of caspase-9, which in turn cleaves and activates pro-caspase into ... caspase-3 and caspase-7 pathway; and by external signals (FAS and TNF), along the caspase 8 pathway. Accessed 25 March 2007. ...
Rho inhibition induces caspase-9 and caspase-3-dependent apoptosis of cultured human endothelial cells. These proteins are ... activates caspase-9 and caspase-3, leading to apoptosis. Although Zamzami et al. suggest that the release of cytochrome c is ... Fesik SW, Shi Y (2001). "Controlling the caspases". Science. 294 (5546): 1477-1478. doi:10.1126/science.1062236. PMID 11711663 ... the caspases. Depending on their function, once activated, Bcl-2 proteins either promote the release of these factors, or keep ...
Cardiolipin Pyroptosis Inflammasome GSDMA GSDMB GSDMC DFNA5 Caspases Caspase-1 Caspase-4 Caspase-5 Caspase-11 Interleukin-1β ... Caspase-11 in mice and its human homolog caspase-4 and -5 are involved in the non-canonical pathway and are activated by ... Several current studies have revealed that GSDMD serves as a specific substrate of inflammatory caspases (caspase-1, -4, -5 and ... Dixit V (2015). "Caspase-11 cleaves gasdermin D for non-canonical inflammasome signaling". Nature. 000. Shi J, Zhao Y, Wang K, ...
Cohen GM (1997). "Caspases: the executioners of apoptosis". Biochem. J. 326 (Pt 1): 1-16. doi:10.1042/bj3260001. PMC 1218630. ... Chua BT, Guo K, Li P (2000). "Direct cleavage by the calcium-activated protease calpain can lead to inactivation of caspases". ...
Cohen GM (1997). "Caspases: the executioners of apoptosis". Biochem. J. 326 (1): 1-16. doi:10.1042/bj3260001. PMC 1218630. PMID ...
Researchers at Columbia University report of reconstituted caspases combined from C. elegans and humans, which maintain a high ... Chelur, Dattananda S.; Chalfie, Martin (February 2007). "Targeted cell killing by reconstituted caspases". Proceedings of the ...
2001). A conserved XIAP-interaction motif in caspase-9 and Smac/Diablo regulates caspase activity and apoptosis. Nature. 410: ... "A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis". Nature. 410 (6824): ... 2001). Isolation and Assay of Caspases. Ch. 1. Methods in Cell Biol. 66:1-27. Profile page at IISER Thiruvananthapuram Faculty ... Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade. Cell, 91(4), 479 ...
Plant cells do not have caspases. Plant disease resistance Phytopathogen Plant hormones Systemic acquired resistance ... the pore-forming activity arises from gasdermin B which is cleaved by caspases as a result of the oligomerisation of the NLRs. ...
Caspases are part of the apoptosis pathway. When BCl-2 decreases, the expression of caspases increases. As a result, apoptosis ...
Excess progenitor cell proliferation that leads to gross brain abnormalities is often lethal, as seen in caspase-3 or caspase-9 ... Kuida, K (1998). "Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9". Cell. 94 (3): 325- ... Pyroptosis, an inflammatory type of cell death, is uniquely mediated by caspase 1, an enzyme not involved in apoptosis, in ... to cells (such as feedback from neighbors, stress or DNA damage), mitochondria release caspase activators that trigger the cell ...
Kroemer G, Martin SJ (2005). "Caspase-independent cell death". Nature Medicine. 11 (7): 725-30. doi:10.1038/nm1263. PMID ... Called "non-apoptotic programmed cell-death" (or "caspase-independent programmed cell-death"), these alternative routes to ...
... caspase-11 or caspase-5 in humans, which is responsible for some of the effects that had been attributed to caspase-1, ... The 2011 paper showed that mice lacking the gene that encodes caspase-1 also carry a mutation in a neighboring caspase gene, ... Dixit was among the first scientists to demonstrate that other immune caspases besides death caspases are incorporated into the ... In particular, caspase-1 activates cytokines of the interleukin-1 family, which are immune effectors that initiate an immune ...
June 2004). "PYNOD, a novel Apaf-1/CED4-like protein is an inhibitor of ASC and caspase-1". Int. Immunol. 16 (6): 777-86. doi: ... 2004). "PYNOD, a novel Apaf-1/CED4-like protein is an inhibitor of ASC and caspase-1". Int. Immunol. 16 (6): 777-86. doi: ... 2005). "PYPAF3, a PYRIN-containing APAF-1-like protein, is a feedback regulator of caspase-1-dependent interleukin-1beta ... caspase-1 and PYCARD. ENSG00000281166, ENSG00000182261 GRCh38: Ensembl release 89: ENSG00000276780, ENSG00000281166, ...
Hair follicles in anaphase express four different caspases. Significant levels of inflammatory infiltrate have been found in ...
Kitagawa K, Niikura Y (Apr 2008). "Caspase-independent mitotic death (CIMD)". Cell Cycle. 7 (8): 1001-5. doi:10.4161/cc.7.8. ...
... initiates caspase-dependent and caspase-independent apoptosis in human cervical carcinoma cells. Pardaxin triggers ... This results in the activation of caspases as well. ROS also causes a caspase independent pathway that results in apoptosis. ... Cyt c activates the caspase chain that leads to apoptosis. ROS also activates the JNK pathway. JNK is phosphorylated, which ... These trigger apoptosis when they enter the nucleus, not needing to involve caspases. Primor N (May 1985). "Pharyngeal cavity ...
... including caspase-1/4/5 in humans and caspase-11 in mice. Pro-apoptotic caspases, including caspase-6/7/8/9, are not required ... Inflammasome activates a different set of caspases as compared to apoptosis, for example, caspase-1/4/5 in humans and caspase- ... of gram-negative bacteria directly onto caspase-4/5 in humans and caspase-11 in murines. Binding of LPS onto these caspases ... Caspase-3, an executioner caspase in apoptosis, can cleave gasdermin E (GSDME) to produce a N-terminal fragment and a C- ...
... 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 ... "Death receptor recruitment of endogenous caspase-10 and apoptosis initiation in the absence of caspase-8". Journal of ... Caspase 8 then cleaves RIPK1, leading to inhibition of this signalling, inhibiting cell death. FADD knockout in mouse embryos ...
Earnshaw, W. C.; Martins, L. M.; Kaufmann, S. H. (1999). "Mammalian caspases: Structure, activation, substrates, and functions ... and used it to identify the first apoptotic caspase substrate. Earnshaw is also an elected Fellow of the Royal Society of ...
... which resembles that of the animal caspases. Similarly to the animal caspases, the phytaspase is a cell death promoting ... In contrast with the animal caspases, that exist in the cytoplasm in a form of pre-synthesized precursors, the activation of ... Porter, A. G.; Jänicke, R. U. (1999-02-01). "Emerging roles of caspase-3 in apoptosis". Cell Death and Differentiation. 6 (2): ... The phytaspase displays a strict substrate specificity, which resembles that of the animal caspase-3. It recognizes a ...
Initiator caspases: responsible for the activation of effector caspases. These caspases are activated through oligomerization ... FLIPL's pseudo-caspase has two tandem DEDs that are very similar to the N-terminus of capase-8, but in which there is an ... Studying caspases is important since they don't only control apoptosis but also inhibit it, depending on the necessity of the ... This type of apoptosis depends on the pDED of the HIP-1, and it consists in the activation of caspase-3, an enzyme that is ...
In caspase-3 the 'hook' and 'sinker' attach. Both the BIR2 and BIR3 have a groove that is predominately negatively charged. ... This is done through the binding to caspases directly. Similar to the functionality of NAIP, the BIR3 domain of XIAP binds to ... This is unexpected because, in nerve growth factor withdrawal, caspase-3 and -9 are activated, causing cell death, which are ... When overexpressed, XIAP is able to block caspases extremely well and prevents cell death of sympathetic neurons when nerve ...
... has been shown to interact with: ALS2CR2, Caspase 3. Caspase 7, Caspase-9, Diablo homolog HtrA serine peptidase 2, MAGED1 ... Caspases are the enzymes primarily responsible for cell death. XIAP binds to and inhibits caspase 3, 7 and 9. The BIR2 domain ... When inhibiting caspase-3 and caspase-7 activity, the BIR2 domain of XIAP binds to the active-site substrate groove, blocking ... This allows normal caspase activity to proceed. The binding process of Smac/DIABLO to XIAP and caspase release requires a ...
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, ...
Wu YM, Huang CL, Kung HJ, Huang CY (2001). "Proteolytic activation of ETK/Bmx tyrosine kinase by caspases". J. Biol. Chem. 276 ...
Valencia CA, Cotten SW, Liu R (Dec 2007). "Cleavage of BNIP-2 and BNIP-XL by caspases". Biochemical and Biophysical Research ...
Caspase-cleaved fragment of keratin 18 = ccK18 Keratin 18 = K18 (or CK18) M30® = the antibody that recognizes a neoepitope on ... Caspases cleave keratin 18 at two sites during apoptosis. Cleavage at Asp396 generates a neo-epitope recognized by the ... Caspases are activated in apoptotic cells and cleave intracellular protein substrates. Keratin 18 (K18) is one such substrate, ... M30 Apoptosense® ELISA is an enzyme-linked immunosorbent assay developed for the detection of soluble caspase-cleaved keratin ...
Johnson CE, Kornbluth S (September 2008). "Caspase cleavage is not for everyone". Cell. 134 (5): 720-1. doi:10.1016/j.cell. ...
p53 binds to the third intron of the caspase 6 gene, and promotes the activation of the gene. Caspase 6 in turn activates HIPK2 ... The activity of HIPK2 is increased through the action of caspase 6. Caspase 6 cleaves HIPK2 at residue D916 and D977. As a ... MacLachlan TK, El-Deiry WS (July 2002). "Apoptotic threshold is lowered by p53 transactivation of caspase-6". Proceedings of ... CREB binding protein p53 p300 SKI protein TP53INP1 ATM kinase PIN1 HMGA1 SIAH1 WSB1 caspase 6 Tachykinin receptor 3 Mdm2 CtBP ...
"Entrez Gene: caspase recruitment domain family". Bertin J, Wang L, Guo Y, Jacobson MD, Poyet JL, Srinivasula SM, Merriam S, ... Caspase recruitment domain-containing protein 14, also known as CARD-containing MAGUK protein 2 (Carma 2), is a protein in the ... This protein is also a member of the CARD-CC protein family, which is defined by carrying a characteristic caspase-associated ... 2001). "Card10 is a novel caspase recruitment domain/membrane-associated guanylate kinase family member that interacts with ...
Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7). Once initiator caspases are activated, they produce a chain reaction ... Caspase-1, Caspase-4, Caspase-5 and Caspase-11 are considered Inflammatory Caspases.[7] ... Caspase-1, Caspase-4 and Caspase-5 in humans, and Caspase-1 and Caspase-11 in mice play important roles in inducing cell death ... or direct activation of Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7) to degrade cellular components as shown in ...
Caspase-9. FADD. Caspase-8. Caspase-3. Caspase-2. Caspase-1. Caspase-11. Caspase-12. Bcl-xL. Bcl-w. Bcl-2(1,2,3). Mcl1. A1. Bax ... Caspase. CARD/DED/BIR. Bcl-2. DD. TNF/TNFR. Kinases. ILs. Viral. Lipid. Engulf. TF. RING. Toll. Other Apop. Other NFkB. ... caspase-9. BIRx3/RING. 19q13.3-q13.4. testis. livin, ML-IAP, KIAP, BIRC7 (human,L). inhibit. caspase-9. BIR/RING. 1. 1. ... caspase-1, RICK. CARD. 1. 11q22. Bimp type. CARD9 [human, (1, 2, 3), rat, carp]. induce. Bcl10. CARD/coiled-coil. 1. 9q34.3. ...
... caspase-2 (20), caspase-3 (21-23), caspase-7 (24-26), caspase-8 (27), and caspase-9 (28). The overall architecture of all ... Caspase structure. (A) The caspase family. Three major groups of caspases are presented. Group I: inflammatory caspases; group ... Caspase signaling. Mechanisms of caspase activation. All caspases are produced in cells as catalytically inactive zymogens and ... activation of effector caspases is inhibited by IAPs (see text). Effector caspases are shown in light green; cellular caspase ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
Caspase-1 cleaves PPARγ for potentiating the pro-tumor action of TAMs. [Nat Commun. 2017] Caspase-1 cleaves PPARγ for ... Caspase-1 as a multifunctional inflammatory mediator: noncytokine maturation roles. [J Leukoc Biol. 2016] Caspase-1 as a ... LSBio CASP1 / Caspase 1 Elisa Kits [LifeSpan BioSciences, Inc.] LSBio CASP1 / Caspase 1 Elisa Kits. LifeSpan BioSciences, Inc. ... LSBio CASP1 / Caspase 1 Antibodies [LifeSpan BioSciences, Inc.] LSBio CASP1 / Caspase 1 Antibodies. LifeSpan BioSciences, Inc. ...
Molecular Docking Analysis of Caspase-3 Activators as Potential Anticancer Agents.. Kashaw SK, Agarwal S, Mishra M, Sau S, Iyer ... Pharmacophore Modeling, Docking and Molecular Dynamics Studies on Caspase-3 Activators Binding at β-Tubulin Site. Bhunia SS et ... Acteoside Binds to Caspase-3 and Exerts Neuroprotection in the Rotenone Rat Model of Parkinsons Disease. Yuan J et al. PLoS ... Pharmacophore modeling and docking studies on some nonpeptide-based caspase-3 inhibitors. Sharma S et al. Biomed Res Int. (2013 ...
... induced cleavage of caspase-3 and increased activity of caspase-3 and caspase-7 (caspase-3/7). Caspases are serine proteases ... Caspase-8 can activate caspase-3/7, and LPS treatment increased caspase-8 activity in BV2 cells, which required Toll-like ... Knocking down caspase-3 or caspase-7 by siRNA inhibited LPS-induced activation. LPS treatment of BV2 cells triggered cell death ... In addition, LPS-induced increases in iNOS abundance were attenuated by coinjection of inhibitors of caspase-8, caspase-3/7, or ...
Caspase activity in microglia does not trigger cell death, but rather induces proinflammatory responses. ... Caspase activity in microglia does not trigger cell death, but rather induces proinflammatory responses. ...
Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... Caspase 10 has been shown to interact with FADD, CFLAR, Caspase 8, Fas receptor, RYBP, TNFRSF1A and TNFRSF10B. The Proteolysis ... Wang, J; Chun H J; Wong W; Spencer D M; Lenardo M J (November 2001). "Caspase-10 is an initiator caspase in death receptor ... This protein cleaves and activates caspases 3 and 7, and the protein itself is processed by caspase 8. Mutations in this gene ...
A) Caspases have been found in organisms ranging fromC. elegans to humans. The 13 identified mammalian caspases (named caspase- ... The precise caspase targets of the IAPs remain elusive. Potent, selective inhibition of caspase-3 and caspase-7 was observed in ... Crystal structures of two active caspases (caspase-1 and caspase-3) have been determined: in both cases, two heterodimers ... What Are Caspases?. Caspases were implicated in apoptosis with the discovery that CED-3, the product of a gene required for ...
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 ...
Caspases are a family of enzymes with very specific characteristics that can be used in almost every biological pathway in the ... Some caspases are activated by fas in the pro-apoptosis cell pathway, and then go on to activate further caspases (caspase 3), ... Research has suggested that activation of caspase 6 is controlled by pro-Caspase-6a, which is in turn controlled by pro-Caspase ... In the same way caspases are activated, many anti-apoptotic molecules can also inhibit caspases to prevent cell death, by a ...
CASPASE-6, HUMAN RECOMBINANT. Highly active caspase-6 (Mch2) from human cDNA, expressed in an E. coli expression system. cDNA ... CASPASE-9, HUMAN RECOMBINANT. Highly active caspase- 9, from human cDNA, expressed in an E. coli expression system. cDNA ... CASPASE-3, RECOMBINANT, HUMAN. Cleaved and activated enzyme formed from the human proenzyme cDNA expressed in E.coli.. ...
Our results demonstrate the importance of caspase-mediated RIPK1 cleavage during embryonic development and show that caspase ... Here we show that the heterozygous missense mutations D324N, D324H and D324Y prevent caspase cleavage of RIPK1 in humans and ... Heterozygous mutateons in the caspase-8 cleavage site of RIPK1 cause a range of autoinflammatory symptoms in humans, and ... as well as by caspase-8-mediated cleavage1-7. The physiological relevance of this cleavage event remains unclear, although it ...
To protect your privacy, your account will be locked after 6 failed attempts. After that, you will need to contact Customer Service to unlock your account.. You have 4 remaining attempts.. You have 3 remaining attempts.. You have 2 remaining attempts.. You have 1 remaining attempt.. Contact Customer Service ...
Because caspase S-nitrosylation is inhibitory (2-4), yet Fas promotes caspase activation, we reasoned that Fas induces caspase ... Decreased caspase-3 S-nitrosylation after Fas activation. (A) Caspase-3 denitrosylation (photolysis). Caspase-3 was ... C) S-nitrosylation-denitrosylation of caspase-3. The NO content of untreated caspase-3 immunoprecipitates (Casp-3), caspase-3 ... To determine if caspase S-nitrosylation was functionally coupled to intracellular caspase activity, we measured caspase-3-like ...
A hierarchy of caspase activation exists whereby initiator caspases become activated to cleave and activate effector caspases. ... caspases (2, 8, 9 and 10) is much longer than that of effector caspases 3, 6 and 7. For the initiator caspases, binding to ... These caspases can either directly activate caspase 3 or signal through the mitochondria via a Bid‐dependent cleavage event. ... Once active, initiator caspases proteolytically cleave effector caspases at distinct aspartate residues, to release the ...
... Nat Rev Immunol. 2006 Nov;6(11):813-22. doi: 10.1038/nri1943. ... Rectification of this apoptotic-inflammatory imbalance using modulators of caspases and other components of the cell-death ...
Caspase-cleaved tau exhibits rapid memory impairment associated with tau oligomers in a transgenic mouse model. Neurobiol Dis. ... Caspase-cleaved tau exhibits rapid memory impairment associated with tau oligomers in a transgenic mouse model. Neurobiol Dis. ... which lacks 20 amino acids at the C-terminus and thus mimics the tau fragment produced by caspase cleavage. Memory deficits ...
Intense research into the signaling pathways of apoptosis has revealed a dominant role for proteases belonging to the caspase ... Caspase 8: igniting the death machine Structure. 1999 Oct 15;7(10):R225-9. doi: 10.1016/s0969-2126(00)80048-9. ... Intense research into the signaling pathways of apoptosis has revealed a dominant role for proteases belonging to the caspase ...
Caspase activity is activity that is caused by a group of very complex enzymes that regulate programmed cell death, or ... To keep confusion to a minimum, caspases are numbered, starting with caspase 1 and going through 12. Given the complexity of ... There are two major classes of caspase activity that activate apoptosis. The first are initiator caspases, which are regulated ... The active initiator caspases cleave the inactive effector caspases, which then activate apoptosis. ...
Compare Caspase Assay from leading suppliers on Biocompare. View specifications, prices, citations, reviews, and more. ... Caspase Assay. A caspase is a type of protease that when activated cleaves protein substrates. This leads to the cell becoming ... Therefore, this makes caspases an ideal biomarker to use to detect apoptosis. The most common caspase assays come in kits and ... Materials: infected or uninfected cells, pan-caspase inhibitor zVAD, and caspase-... Read Review ...
Executioner caspases have only rarely been found mutated or silenced, and also initiator caspases are only affected in ... Second, in tumor cells caspases might be kept in check by cellular caspase inhibitors such as c-FLIP or XIAP. Third, pathways ... Finally, caspase-independent cell death mechanisms might abrogate the selection pressure for caspase inactivation during tumor ... There is experimental evidence from transgenic mice that certain initiator caspases, such as caspase-8 and -2, might act as ...
Although Dredd, by homology to the human caspases-8 and -10, is thought to be an initiator rather than an effector caspase, it ... The direct involvement of a caspase in Relish endoproteolysis represents a novel mechanism of NF-κB activation and caspase ... a role for a caspase in Relish activation was indicated by the fact that mutants in Dredd, a Drosophila caspase gene, are ... Caspase-mediated processing of the Drosophila NF-κB factor Relish. Svenja Stöven, Neal Silverman, Anna Junell, Marika Hedengren ...
The caspase-deficient NB7 neuroblastoma cells have been described in ref. 34. Caspase-8-deficient and reconstituted Jurkat ... Caspase-3 (MAB4703, 1:500; Chemicon), caspase 9 (sc17784, 1:100; Santa Cruz Biotechnology), actin (1:5,000; Sigma), and PARP ( ... H) NB7 neuroblastoma cells lacking caspase 8 (filled bar) or NB7C8 cells reconstituted for caspase 8 expression (open bars) ... Sensitivity to ScA was significantly increased among cells expressing caspase 8, whereas siRNA knockdown of caspase 8 increased ...
Caspase-3 activation and function have been well-defined during programmed cell death, but caspase activity, at low levels, is ... Caspase-3 activation and function have been well-defined during programmed cell death, but caspase activity, at low levels, is ... Caspase-3 subunit p17. A. 175. Homo sapiens. Mutation(s): 1 Gene Names: CASP3, CPP32. EC: 3.4.22.56. ... Caspase-3 subunit p12. B. 102. Homo sapiens. Mutation(s): 0 Gene Names: CASP3, CPP32. EC: 3.4.22.56. ...
We have expressed the putative caspase‐like gene MaOC 1 from the toxic bloom‐forming cyanobacterium M icrocystis aeruginosa PCC ... Caspases are a family of cysteine‐dependent proteases known to be involved in the process of programmed cell death in metazoans ... Recently, cyanobacteria were also found to contain caspase‐like proteins, but their existence has only been identified in ... Due to their structural and functional differences to other known caspase‐like proteins, we suggest to name these evolutionary ...
Phage display reveals peptides that bind to the caspase-6 zymogen, inducing its tetramerization and specifically inhibiting its ... Rare human Caspase-6-R65W and Caspase-6-G66R variants identify a novel regulatory region of Caspase-6 activity *Agne ... Allosteric peptides bind a caspase zymogen and mediate caspase tetramerization. *Karen Stanger1. *, Micah Steffek2. n5*, Lijuan ... Self-activation of caspase-6 in vitro and in vivo: caspase-6 activation does not induce cell death in HEK293T cells. . Biochim ...
Therefore, downstream signaling molecules, such as caspase-1, caspase-3, caspase-7, or caspase-9 can bypass most of these road ... such as caspase-1, caspase-3, and caspase-9 (data not shown for caspase-9), can trigger apoptosis in a wide panel of prostate ... activation of caspase-1, caspase-3, caspase-7, and caspase-9 by CID can be achieved at expression levels and CID concentrations ... caspase-1, caspase-3, and caspase-8 and found that multiple prostate tumor cell lines are insensitive to the upstream signaling ...
  • Activation involves dimerization and often oligomerisation of pro-caspases, followed by cleavage into a small subunit and large subunit. (wikipedia.org)
  • Cleavage of the procaspase at the specific Asp-X bonds leads to the formation of the mature caspase, which comprises the heterotetramer p20 2 -p10 2 , and the release of the prodomain. (jci.org)
  • Treatment of mouse microglia BV2 cells with lipopolysaccharide (LPS) induced cleavage of caspase-3 and increased activity of caspase-3 and caspase-7 (caspase-3/7). (sciencemag.org)
  • Activation of protein kinase C δ (PKCδ) by caspase-3/7-mediated cleavage was required for LPS-induced activation of BV2 cells. (sciencemag.org)
  • CAD release from ICAD inhibition is achieved by cleavage of ICAD at these Asp residues by the caspase-3. (wikipedia.org)
  • Our results demonstrate the importance of caspase-mediated RIPK1 cleavage during embryonic development and show that caspase cleavage of RIPK1 not only inhibits necroptosis but also maintains inflammatory homeostasis throughout life. (nature.com)
  • Fig. 1: Heterozygous mutations of the RIPK1 caspase-8 cleavage site cause autoinflammatory disease. (nature.com)
  • Fig. 2: Homozygous mutation of the RIPK1 caspase-8 cleavage site in mice causes early embryonic lethality. (nature.com)
  • Fas therefore activates caspase-3 not only by inducing the cleavage of the caspase zymogen to its active subunits, but also by stimulating the denitrosylation of its active-site thiol. (sciencemag.org)
  • Caspase‐mediated cleavage of target proteins may produce stable functional effector fragments or unstable fragments that are quickly degraded. (els.net)
  • For the initiator caspases, binding to adaptor proteins results in the cleavage of the prodomain and subsequent rearrangement of the large and small subunits to produce a catalytically active heterodimer. (els.net)
  • These caspases can either directly activate caspase 3 or signal through the mitochondria via a Bid‐dependent cleavage event. (els.net)
  • Functional outcomes of caspase‐mediated cleavage. (els.net)
  • Following cleavage of a target protein by effector caspases, there are several probable functional consequences. (els.net)
  • a) Caspase‐mediated cleavage of intracellular proteins may result in the production of stable, functionally active effector fragments. (els.net)
  • These effector fragments may become newly active (as in the case of caspase‐mediated cleavage of ROCK1) or may act to inhibit normal protein function (e.g. caspase‐mediated cleavage of IKB renders the protein resistant to proteosomal degradation and thus allows for sustained inhibition of NFκB, see text for details). (els.net)
  • These mice express a truncated form of human tau protein called TauC3, which lacks 20 amino acids at the C-terminus and thus mimics the tau fragment produced by caspase cleavage. (alzforum.org)
  • Here we used mutational analysis and protein microsequencing to demonstrate that a caspase target site, located in the linker region between the Rel and the IκB-like domain, is the site of signal-dependent cleavage. (pnas.org)
  • We report the actual cleavage site and direct interactions between Dredd and Relish, which together provide strong evidence that Relish endoproteolysis is indeed carried out by the caspase Dredd. (pnas.org)
  • Coupling Caspase Cleavage and Proteasomal Degradation of Proteins. (ingentaconnect.com)
  • Caspases are cysteinyl aspartate proteases that control diverse signaling pathways, promoting the cleavage at one or two sites of hundreds of structural and regulatory protein substrates. (ingentaconnect.com)
  • Caspase cleavage sites are commonly found within PEST motifs, which are segments rich in proline (P), glutamic acid (D), aspartic acid (E) and serine (S) or threonine (T) residues. (ingentaconnect.com)
  • Considering that Nand C- terminal peptide carrying PEST motifs form disordered loops in the globular proteins after caspase cleavage, it is postulated here that these exposed termini serve as unstructured initiation site, coupling caspase cleavage and ubiquitinproteasome dependent and independent degradation of short-lived proteins. (ingentaconnect.com)
  • Caspases belong to a class of specific Cys proteases that show a high degree of specificity with an absolute requirement for cleavage adjacent an Asp residue and a recognition sequence of at least four amino acids N-terminal to this cleavage site. (plantphysiol.org)
  • Cleavage of a caspase molecule yields a large (α) subunit and a small (β) subunit that form the enzymatically active heterodimer. (plantphysiol.org)
  • Caspases can be detected via immunoprecipitation, immunoblotting techniques using caspase specific antibodies, or by employing fluorochrome substrates which become fluorescent upon cleavage by the caspase. (bio-medicine.org)
  • Activation of caspases during apoptosis results in the cleavage of critical cellular substrates, including poly(ADP-ribose) polymerase and lamins, so precipitating the dramatic morphological changes of apoptosis. (portlandpress.com)
  • Cleavage by granzyme B, caspase-6, caspase-8 and caspase-10 generates the two active subunits. (abcam.com)
  • Activation of caspase-3 requires cleavage at Asp175 into the activated p17/p19 and p12 protein fragments. (cellsignal.com)
  • CST Cleaved Caspase-3 (Asp175) (5A1E) Rabbit mAb #9664 recognizes the activated large fragment after cleavage (seen as a 17 kDa and 19 kDa doublet on western blot). (cellsignal.com)
  • CST Cleaved Caspase-3 (Asp175) (5A1E) Rabbit mAb #9664 recognizes the activated large fragment after cleavage (seen as a 17 kDa and 19 kDa doublet). (cellsignal.com)
  • Caspases are present as inactive pro-enzymes that are activated by proteolytic cleavage. (biovision.com)
  • Caspase 8 and caspase 9 activate caspase 3 by proteolytic cleavage and caspase 3 then cleaves vital cellular proteins or other caspases. (biovision.com)
  • Caspases have a precursor form composed of a prodomain, and large and small catalytic subunit, and are activated through a cleavage adjacent to an aspartate to liberate units and allow formation of an a2b2 tetramer. (novusbio.com)
  • In the study, researchers confirmed that the deadly cleavage is caused by a key enzyme called caspase-6. (rxpgnews.com)
  • Parasitic infection dose dependently diminished cleavage of caspase 8, the BH3-only protein Bid, and the downstream caspases 9 and 3. (curehunter.com)
  • Caspases are a group of signaling proteins that have proteolytic function, and drive apoptosis through a chain of cleavage events. (biolegend.com)
  • Once activated through cleavage, caspase-9 activates the downstream effector caspase-3 that irreversibly causes apoptosis [ 20 ]. (hindawi.com)
  • Cleavage of pNA peptides by caspases generates pNA that is monitored colorimetrically at ~405 nm. (anaspec.com)
  • Cleavage of caspase-12 at Asp94, mediated by endoplasmic reticulum stress (ERS), contributes to stretch-induced apoptosis of myoblasts. (addgene.org)
  • Intermediate caspase-9 cleavage forms may also be seen at ~21 kDa. (novusbio.com)
  • Background: Caspase-3 (CPP-32, Apoptain, Yama, SCA-1) is a critical executioner of apoptosis, as it is either partially or totally responsible for the proteolytic cleavage of many key proteins, such as the nuclear enzyme poly (ADP-ribose) polymerase (PARP) (1). (cellsignal.com)
  • Cleavage of caspase-3 requires the aspartic acid residue at the P1 position (2). (cellsignal.com)
  • The assay kits detect caspase activation by assaying for the cleavage of a fluorescent or a colorimetric substrate. (clontech.com)
  • The Caspase-3 Colorimetric Assays measure the proteolytic cleavage of the chromophore p-nitroanilide (pNA) by caspase-3. (clontech.com)
  • I have tried western blotting for IL-1beta maturation and caspase-1 cleavage. (protocol-online.org)
  • Further, DNA degradation in caspase-1-dependent cell death is independent of ICAD cleavage, which is the substrate of caspase-3 and further supports the lack of caspase-3 involvement. (protocol-online.org)
  • Now, Zhao and colleagues report that a product resulting from caspase-2 cleavage of tau resists fibrillation, promotes synaptic dysfunction, and results in neurodegeneration in mice. (sciencemag.org)
  • The investigators showed that caspase-2 cleavage of tau at Asp314 resulted in a truncation product, ∆tau314, which was present at higher levels in the brains of AD mice compared with wild-type control animals. (sciencemag.org)
  • The improvements in memory function corresponded to a reduction in ∆tau314, linking the tau caspase-2 cleavage product to neurodegenerative behavioral deficits in vivo. (sciencemag.org)
  • Caspase-2 cleavage of tau reversibly impairs memory. (sciencemag.org)
  • Preventing caspase-2 cleavage of tau blocks memory impairment in an animal model of Alzheimer's disease. (sciencemag.org)
  • As the name suggests, caspases cleave their substrates after an aspartate residue (in P1 position in the cleavage site). (frontiersin.org)
  • Furthermore, TAIII induced apoptosis of HL-60 cells through caspase-3, caspase-8, and caspase-9 activations and PARP cleavage in a dose- and time-dependent manner. (springer.com)
  • Q-VD-OPh prevents caspase mediated cleavage of PARP and activation of the major initiator and effector caspases. (selleckchem.com)
  • Caspases, a family of cysteine proteases, play a central role in apoptosis. (jci.org)
  • These changes reflect complex biochemical events carried out by a family of cysteine proteases called caspases. (sciencemag.org)
  • Recent studies suggest that this inhibition is achieved, at least in part, by S-nitrosylation of the active-site cysteine of caspases, a family of cysteine proteases that execute the death program ( 2-4 ). (sciencemag.org)
  • Caspases are a family of cysteine‐dependent proteases known to be involved in the process of programmed cell death in metazoans. (ingentaconnect.com)
  • Caspases, a family of cysteine proteases, are the central regulators of apoptosis. (cellsignal.com)
  • Caspase 7 (also known as CASP7, Mch3, ICE-LAP3, CMH-1) is a member of caspase family of cysteine proteases. (novusbio.com)
  • Background -Z-Val-Ala-Asp(OMe)-CH 2 F (ZVAD-fmk), a tripeptide inhibitor of the caspase interleukin-1β-converting enzyme family of cysteine proteases, may reduce myocardial reperfusion injury in vivo by attenuating cardiomyocyte apoptosis within the ischemic area at risk. (ahajournals.org)
  • Using antisera specific for the activated forms of caspases, the family of cysteine proteases that underlies apoptosis, we demonstrated that active forms of initiator and effector caspases are selectively localized at the NMJ in SCS. (sigmaaldrich.com)
  • Per usual in non-apoptotic growing cells caspase activated dnase is held in check inactivated in the cytoplasm thanks to the association with its inhibitor, inhibitor of caspase-activated DNase (ICAD) also known as DNA fragmentation factor 45 kDa (DFF45). (wikipedia.org)
  • This is an Investigator Initiated, Phase I/II study, where Type 1 diabetic participants will receive a 14 day oral treatment of the investigational caspase inhibitor drug IDN-6556 following their first islet transplant. (clinicaltrials.gov)
  • The primary objective of this protocol is to assess the safety of the IDN-6556 caspase inhibitor in adult Type 1 diabetic participants receiving their first islet transplant. (clinicaltrials.gov)
  • 14 day oral treatment of the investigational caspase inhibitor drug IDN-6556 following first islet transplant at 50mg twice daily. (clinicaltrials.gov)
  • The caspase-8 inhibitor FLIP promotes act. (mendeley.com)
  • Results: Under conditions in which proliferation of CD3-activated human T lymphocytes is increased by recombinant FasL, there was activation of the transcription factors NF-κB and AP-1 and recruitment of the caspase-8 inhibitor and FADD-interacting protein FLIP (FLICE-like inhibitory protein). (mendeley.com)
  • Caspase 3 is a cytoplasmic caspase with two isoforms (one acts as a dominant negative inhibitor), and is involved in the activation cascade for apoptosis execution. (novusbio.com)
  • Adding the caspase inhibitor ZVAD blocked early apoptotic cell death but revealed the presence of necrotic cell death at 48 hours. (medicalnewstoday.com)
  • According to Dr. Ding, "We still don't know the mechanism underlying caspase inhibitor-induced necrosis of the liver. (medicalnewstoday.com)
  • To test for caspase dependent TH-ir cell loss, the pancaspase inhibitor ZVAD ( N -benzyloxycabonyl-Val-Ala-Asp-fluoromethylketone) was used to rescue TH-ir cells from estradiol-mediated reduction in number. (jneurosci.org)
  • ZVAD-fmk (fluoro-methylketone), a tripeptide inhibitor of the caspase, is reported to attenuate cardiomyocyte apoptosis in vitro. (ahajournals.org)
  • Molecular model of caspase-1 complexed with an inhibitor. (sciencephoto.com)
  • Q-VD-Oph (Quinoline-Val-Asp-Difluorophenoxymethylketone) is a potent pan- caspase inhibitor with IC50 ranged from 25 to 400 nM for caspases 1,3,8, and 9. (selleckchem.com)
  • In the present study, we used SB203580, a p38MAPK inhibitor, and Z-LETD-FMK, a caspase-8 inhibitor, to determine the relation of p38MAPK and caspase-8 in the apoptosis process induced by DATS. (scielo.br)
  • Tumour growth can occur by a combination of factors, including a mutation in a cell cycle gene which removes the restraints on cell growth, combined with mutations in apoptopic proteins such as Caspases that would respond by inducing cell death in abnormally growing cells. (wikipedia.org)
  • The activation of initiator caspases and inflammatory caspases is initiated by dimerisation, which is facilitated by binding to adaptor proteins via protein-protein interaction motifs that are collectively referred to as death folds. (wikipedia.org)
  • Caspase-3 was efficiently immunoprecipitated with its specific antibody, but not with control antibody ( Fig. 1 B). Silver stains revealed that associated proteins did not significantly contaminate the caspase immunoprecipitates. (sciencemag.org)
  • Proteins were immunoprecipitated from 10C9 cell lysates using a caspase-3-specific monoclonal antibody (Caspase-3 IP), or with equal concentrations of an isotype-matched control antibody (Control IP). (sciencemag.org)
  • The proteins that execute the apoptotic programme are a group of proteases termed caspases (cysteine‐dependent aspartate‐specific protease). (els.net)
  • Substrates targeted by caspases during the apoptotic programme include proteins involved in maintaining various aspects of cytoskeletal and organelle architecture as well as proteins that function in signalling networks critical for cell function. (els.net)
  • Apoptotic caspases are cysteine proteases that become activated in response to diverse extracellular and intracellular stimuli and subsequently carry out the cell death programme by systematically cleaving intracellular proteins. (els.net)
  • Once active, caspase 9 functions to proteolytically cleave and activate the effector caspases 3 and 7, which then go on to cleave numerous intracellular proteins to dismantle the cell. (els.net)
  • Recently, cyanobacteria were also found to contain caspase‐like proteins, but their existence has only been identified in silico up to now. (ingentaconnect.com)
  • In contrast to plant or metazoan caspase‐like proteins, whose activity is calcium‐dependent or requires dimerisation for activation, MaOC1 was activated by autocatalytic processing after residue Arg219, which separated the catalytic domain and the remaining 55 kDa subunit. (ingentaconnect.com)
  • Due to their structural and functional differences to other known caspase‐like proteins, we suggest to name these evolutionary primitive proteins orthocaspases. (ingentaconnect.com)
  • In general, apoptotic cell death involves a sequence of caspase activation events in which initiator caspases activate downstream executioner caspases that process a variety of target proteins eventually leading to the apoptotic phenotype. (plantphysiol.org)
  • Once activated, initiation caspases cleave and activate downstream effector caspases (including caspase-3, -6, and -7), which in turn execute apoptosis by cleaving targeted cellular proteins. (cellsignal.com)
  • Adaptor proteins like FAS-associated death domain (FADD) and TNFR-associated death domain (TRADD) then facilitate the recruitment and dimerization of procaspase-8, forming the active dimeric caspase-8. (biolegend.com)
  • Caspase-12 is co-localized to the ER with several proteins that are involved in Alzheimer's disease including -gamma-secretase presenilin and beta-amyloid precursor protein (APP). (thermofisher.com)
  • In the extrinsic way, the apoptotic signal begins by the union of extra cellular ligands to the surface of cell receptors, resulting in a recruitment of the cytosolic adapter of proteins, that activates the caspase-8 or caspase-10 initiator, and subsequently, the caspases effectors -3, -7 and possibly -6. (thefreedictionary.com)
  • you can check caspase-3 activation or other proteins to make sure cell death pathways are activated. (protocol-online.org)
  • In non-neuronal cells the PIDDosome, composed of caspase 2 and two death adaptor proteins, PIDD (p53-inducible protein with a death domain) and RAIDD {RIP (receptor-interacting protein)-associated ICH-1 [ICE (interleukin-1β-converting enzyme)/CED-3 (cell-death determining 3) homologue 1] protein with a death domain}, has been proposed as the caspase 2 activation complex, although the absolute requirement for the PIDDosome is not clear. (sigmaaldrich.com)
  • Caspase-1 is a protease, an enzyme that cleaves proteins. (sciencephoto.com)
  • Additionally we are shipping Caspase 9 Kits (75) and Caspase 9 Proteins (20) and many more products for this protein. (antibodies-online.com)
  • The knock-on effects of the action of caspases keep us alive, initiating many vital cellular pathways. (bioportfolio.com)
  • Some caspases are activated by fas in the pro-apoptosis cell pathway, and then go on to activate further caspases (caspase 3), which induce apoptosis, while others interact with Apaf-1 in other cell pathways. (bioportfolio.com)
  • Activation of caspases through intrinsic and extrinsic death pathways. (els.net)
  • Third, pathways upstream of caspase activation might be disrupted in tumor cells. (mdpi.com)
  • Although ScA initiates apoptosis via both the intrinsic and extrinsic pathways, the more sensitive pathway involves activation of caspase 8, which requires concentrations in the low nanomolar range and below, to initiate alterations in the cell membrane and apoptosis. (pnas.org)
  • Caspases 8, 9, 12 and 3 are situated at pivotal junctions in apoptosis pathways. (biovision.com)
  • All three caspase pathways lead to caspase-3 activation. (biovision.com)
  • A liver cell can die in many different ways, but caspase-dependent apoptosis and caspase-independent necrosis are the predominant cell death pathways that contribute to liver injury," explained Dr. Ding. (medicalnewstoday.com)
  • The death receptor and mitochondrion pathways are the mains, in which the key apoptotic proteases capase-8 and caspase-9, respectively, are involved. (thermofisher.com)
  • Activation of caspases plays a major role in the recognized death pathways used by the immune system to control T cell responses and apparently also in killing of target cells by CTLs ( 1 , 32 ). (jimmunol.org)
  • It cleaves and activates caspase-3, -4, -6, -7, -8 and -9, is recruited to Fas- and TNFR-1 receptors in a FADD-dependent manner, and may participate in the granzyme B apoptotic pathways. (thefreedictionary.com)
  • All different pathways end up with activation of caspase-3. (protocol-online.org)
  • This review covers what is known about caspase-like enzymatic activities during plant ER stress-induced PCD and discusses possible regulation pathways leading to the activation of relevant proteases in plants. (frontiersin.org)
  • Among PCD regulators, caspases are central components that mediate animal PCD pathways in response to various stimuli, including ER stress. (frontiersin.org)
  • Caspases ( c ysteine- asp artic prote ases , c ysteine asp art ases or c ysteine-dependent asp artate-directed prote ases ) are a family of protease enzymes playing essential roles in programmed cell death (including apoptosis , pyroptosis and necroptosis ) and inflammation . (wikipedia.org)
  • They are named caspases due to their specific cysteine protease activity - a cysteine in its active site nucleophilically attacks and cleaves a target protein only after an aspartic acid residue. (wikipedia.org)
  • Caspases (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases) are a family of protease enzymes playing essential roles in programmed cell death. (wikipedia.org)
  • This gene encodes a protein that is a member of the cysteine-aspartic acid protease (caspase) family. (wikipedia.org)
  • A caspase is a type of protease that when activated cleaves protein substrates. (biocompare.com)
  • Caspase 9 activates disassembly in response to agents or insults that trigger the release of cytochrome c from mitochondria and is activated when complexed with apoptotic protease activating factor 1 (APAF-1) and extra-mitochondrial cytochrome c. (biovision.com)
  • Caspase-8 (Casp-8), a key protease in the extrinsic cell death-signaling pathway, regulates cell death via both apoptosis and necroptosis. (jci.org)
  • Cell death via apoptosis is a basic cellular function occurring through the cell death receptor family and their ligands which signal through downstream adaptor molecules and the caspase protease family. (novusbio.com)
  • Caspase 9 (also termed ICE-LAP6, Mch6, Apaf-3) is a member of cysteine protease family of caspases and is encoded by the CASP9 gene in humans. (novusbio.com)
  • The caspases are a group of cysteine protease enzymes essential to apoptosis, inflammation and necrosis. (novusbio.com)
  • Caspase 9 (ICE-like apoptotic protease 6, ICE LAP6, apoptotic protease Mch6, apoptotic protease activating factor 3, Apaf3) is a member of the peptidase family C14 that contains a CARD domain. (fishersci.com)
  • Binding of caspase-9 to Apaf- 1 leads to activation of the protease which then cleaves and activates caspase-3. (fishersci.com)
  • A gene on chromosome 2q33-q34 that encodes a protein belonging to the cysteine-aspartic acid protease (caspase) family which, once activated by proteolytic processing, plays a central role in the execution-phase of cell apoptosis, as well as various stages of embryological development. (thefreedictionary.com)
  • The caspase inhibitors, that is, ICE-like protease inhibitors, 11 interfere with apoptosis at a point subsequent to the initiation of the proapoptotic process in cells that have already received apoptosis-promoting signals. (ahajournals.org)
  • Knockout of caspase-8 , a cysteine protease that participates in the signaling for cell death by receptors of the TNF/nerve growth factor family, is lethal to mice in utero. (jimmunol.org)
  • The caspase cysteine protease family is known mainly for the participation of some of its members in programmed cell death in eukaryotes ( 2 ). (jimmunol.org)
  • The ApoAlert Caspase Assay Kits provide a simple and convenient way to detect caspase protease activity using fluorometric or colorimetric methods. (clontech.com)
  • This protein cleaves and activates caspases 3 and 7, and the protein itself is processed by caspase 8. (wikipedia.org)
  • Truncated Bid (tBid) then activates Bax/Bak which induce mitochondrial permeabilisation, the release of cytochrome c , formation of the apoptosome and the activation of caspases 9 and 3. (els.net)
  • Apoptosis induced by CD95 (Fas/APO-1) and tumour necrosis factor activates caspase-8 (MACH/FLICE/Mch5), which contains an N-terminus with FADD (Fas-associating protein with death domain)-like death effector domains, so providing a direct link between cell death receptors and the caspases. (portlandpress.com)
  • Cleaves and activates caspase-6, -7 and -9. (abcam.com)
  • Since TCDD activates caspase 3 after 4 h of infection, we have hypothesized an involvement of BHV-1 infected cell protein 0 (bICP0) in this process. (curehunter.com)
  • Caspase 9 is involved in the caspase activation cascade responsible for apoptosis execution and cleaves/activates Caspase 3 and Caspase 6. (fishersci.com)
  • These results have a similar profile for Caspase 9 , in which tiliroside activates Caspase 9 and doxorubicin did not activate it. (thefreedictionary.com)
  • This is through the release of Cytochrome c from mitochondria is a central event in the death receptor-independent, "intrinsic," apoptotic pathway which facilitates activation by Caspase 9 of the effector Caspases [1], which subsequently activates Caspase 3, and ultimately leads to the apoptotic cell death. (thefreedictionary.com)
  • The results indicated that DATS activates p38MAPK and caspase-8, but both inhibitors have an effect on P38MAPK and caspase-8 activity. (scielo.br)
  • Caspases are a family of enzymes with very specific characteristics that can be used in almost every biological pathway in the body. (bioportfolio.com)
  • Caspase-3 zymogens were found to be S-nitrosylated on their catalytic-site cysteine in unstimulated human cell lines and denitrosylated upon activation of the Fas apoptotic pathway. (sciencemag.org)
  • Caspase activation may proceed through either an external (extrinsic) or internal (intrinsic) death pathway, dependent on the stimulus. (els.net)
  • Rectification of this apoptotic-inflammatory imbalance using modulators of caspases and other components of the cell-death pathway have shown striking efficacy in stringent animal models of sepsis, indicating an entirely novel path forward for the clinical treatment of human sepsis. (nih.gov)
  • Loss of the initiator caspase of the intrinsic apoptotic pathway, caspase-9, however, did not promote cellular transformation. (mdpi.com)
  • The selective activation of the caspase 8 pathway by a small molecule is promising, because few currently used anticancer agents have this property. (pnas.org)
  • This pathway bypasses the need for activated caspase 3 in these cells. (nih.gov)
  • Caspase-9 is involved in mitochondrial apoptosis pathway and is an initiator caspase. (novusbio.com)
  • Growth factor stimulation normally suppresses the intrinsic caspase pathway through PI3K signaling, but loss of this stimulus or the presence of other cellular stresses can activate the intrinsic caspase cascade. (biolegend.com)
  • These findings reveal a novel cell death pathway that neither requires nor induces caspase-3 activation, and suggest that NBs participate in the control of cell survival. (biomedsearch.com)
  • The endoplasmic reticulum (ER) stress is the third apoptotic pathway and caspase-12 is involved. (thermofisher.com)
  • In this study, we demonstrate that engagement of distinct epitopes on CD99 rapidly induces T cell death by a novel caspase-independent pathway. (jimmunol.org)
  • However, the timing or activation sequence of these initiator caspases, which trigger apoptotic pathway, is unclear. (spie.org)
  • Hispolon induces apoptosis through JNK1/2-mediated activation of a caspase-8, -9, and -3-dependent pathway in acute myeloid leukemia (AML) cells and inhibits AML xenograft tumor growth in vivo. (springer.com)
  • Subsequently, active caspases specifically process various substrates that are implicated in apoptosis and inflammation. (jci.org)
  • Caspases proteolytically cleave a host of cellular substrates at aspartate residues, which may render them either functionally inactive or confer novel activities that help to promote cellular demise. (els.net)
  • Using a series of caspase inhibitors with overlapping specificities, enzyme-specific chromogenic substrates, and an antibody specific for activated caspase 7, we have determined that apoptosis in MCF-7 cells proceeds via sequential activation of caspases 9, 7 and 6. (nih.gov)
  • Caspase-8 goes on to cleave the executioner caspases (3, 6, 7), which will cleave substrates like Lamin and Rb to result in DNA fragmentation and apoptosis. (biolegend.com)
  • pNA (4-nitroaniline)-derived caspase substrates are widely used for the colorimetric detection of various caspase activities. (anaspec.com)
  • Caspases are cysteine proteases, expressed as inactive precursors, that mediate apoptosis by proteolysis of specific substrates. (fishersci.com)
  • Structure of caspase-1 (CASP1), originally called interleukin-1 beta-converting enzyme (ICE), the first human caspase to be identified. (wikipedia.org)
  • The active enzyme often exists as a heterotetramer in the biological environment, where a pro-caspase dimer is cleaved together to form a heterotetramer. (wikipedia.org)
  • Caspase-10 is an enzyme that, in humans, is encoded by the CASP10 gene. (wikipedia.org)
  • 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. (wikipedia.org)
  • Caspases were implicated in apoptosis with the discovery that CED-3, the product of a gene required for cell death in the nematode Caenorhabditis elegans , is related to mammalian interleukin-1β-converting enzyme (ICE or caspase-1) ( 2 , 3 ). (sciencemag.org)
  • The presence of Thr 152 in the conserved loop introduces a "kill switch" in mammalian caspase-3, whereas the more ancient Ser 150 reduces without abolishing enzyme activity. (rcsb.org)
  • The crystal structures of both caspase-1 and caspase-3 show that the active enzyme is a heterotetramer, containing two small and two large subunits. (portlandpress.com)
  • Homology between the sense portion of the siRNA sequence and the mRNA enables the nuclease enzyme to bind and cleave the caspase transcript into small pieces, which are degraded by the cell's machinery. (abcam.com)
  • A subtype of caspases that contain long pro-domain regions that regulate the activation of the enzyme. (curehunter.com)
  • Many acute and chronic liver diseases, including alcoholic hepatitis , result from apoptotic (programmed) cell death mediated by the enzyme caspase. (medicalnewstoday.com)
  • 1998). Enzymatic activity of two caspases related to interleukin-1beta-converting enzyme. (anaspec.com)
  • 2000). Caspase 8: an efficient method for large-scale autoactivation of recombinant procaspase 8 by matrix adsorption and characterization of the active enzyme. (anaspec.com)
  • In contrast, diabetic sensory neurons had elevated expression of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP) in their nuclei, cytoplasm, and proximal axonal segments not overlapping with caspase-3 localization. (diabetesjournals.org)
  • However, application of the conditional knockout approach to investigate the cause of death of caspase-8 knockout embryos revealed that this enzyme also serves cellular functions that are nonapoptotic. (jimmunol.org)
  • Due to this activity caspase-1 is also known as ICE (interleukin-1-beta converting enzyme). (sciencephoto.com)
  • Caspase is an inactive enzyme zymogen under normal circumstances, but once activated it will trigger the caspase cascade, eventually leading to apoptosis. (scielo.br)
  • The central component of this machinery is a proteolytic system involving a family of proteases called caspases. (sciencemag.org)
  • Because relatively little is known about caspase regulation, it is instructive to first review lessons learned from well-studied proteolytic systems, which provide a framework for understanding the biology of caspases and can serve as guiding principles for ongoing research in this area. (sciencemag.org)
  • It is tempting to speculate that comparable caspase-mediated proteolytic events cause the apoptotic phenotype observed in dying plant cells. (plantphysiol.org)
  • Caspases are synthesized as inactive pro-enzymes and are activated by directed proteolysis that removes the N-terminal peptide and cleaves the proteolytic domain at specific recognition sites (Fig. 1 ). (plantphysiol.org)
  • The central component of this process is a cascade of proteolytic enzymes called caspases. (bio-medicine.org)
  • In apoptosis, caspases are responsible for proteolytic cleavages that lead to cell disassembly (effector caspases), and are involved in upstream regulatory events (initiator caspases). (bio-medicine.org)
  • In common with other proteases, caspases are synthesized as precursors that undergo proteolytic maturation, either autocatalytically or in a cascade by enzymes with similar specificity. (bio-medicine.org)
  • Activation of caspase-3 requires proteolytic processing of its inactive zymogen into activated p17 and p12 fragments. (cellsignal.com)
  • Caspase-activated DNase (CAD) or DNA fragmentation factor subunit beta is a protein that in humans is encoded by the DFFB gene. (wikipedia.org)
  • Caspase 3 is responsible for cellular differentiation, although it is unclear how this kind of protein can promote the cell apoptosis. (wikipedia.org)
  • Caspase-3 levels in the immunoprecipitates were visualized by protein immunoblot using a caspase-3-specific antibody ( 5 ). (sciencemag.org)
  • Phosphorylation of caspase-3 at a conserved allosteric site by p38-MAPK (mitogen-activated protein kinase) promotes survival in human neutrophils, and the modification of the loop is thought to be a key regulator in many developmental processes. (rcsb.org)
  • Background: Activation of Fas (CD95) by its ligand (FasL) rapidly induces cell death through recruitment and activation of caspase-8 via the adaptor protein Fas-associated death domain protein (FADD). (mendeley.com)
  • The importance of caspase prodomains in the regulation of apoptosis is further highlighted by the recognition of adapter molecules, such as RAIDD [receptor-interacting protein (RIP)-associated ICH-1/CED-3-homologous protein with a death domain]/CRADD (caspase and RIP adapter with death domain), which binds to the prodomain of caspase-2 and recruits it to the signalling complex. (portlandpress.com)
  • Recombinant full length protein corresponding to Human Caspase-3. (abcam.com)
  • We determined mRNA and protein expression of apoptotic markers as well as caspase-3 activity. (hindawi.com)
  • SCs cultured in insulin deprivation demonstrated a significant decrease on mRNA levels of p53, Bax, caspase-9, and caspase-3 followed by a significant increase of Bax and decrease of caspase-9 protein levels relatively to the control. (hindawi.com)
  • Caspase 12 degrades IkappaBalpha protein and enhances MMP-9 expression in human nasopharyngeal carcinoma cell invasion. (addgene.org)
  • Ligands of the TNF superfamily initiate death signaling by inducing receptor oligomerization, recruitment of distinct adapter molecules such as Fas-associated death domain protein for Fas, DR4, and DR5 ( 33 , 34 ) and both Fas-associated death domain protein and TNFR-associated death domain protein for TNFRI/p55 ( 35 ) to the death domain of the receptors and subsequent activation of caspases ( 1 ). (jimmunol.org)
  • CASP10 is an initiator-type caspase which is activated by, and interacts with, upstream adaptor molecules through CARD and DED protein-protein interaction domains. (thefreedictionary.com)
  • Two FRET probes were constructed that each encoded a CRS (caspase-2 or caspase-9 recognition Site) fused with a cyan/yellow fluorescent protein (CFP/YFP) and a red fluorescent protein (DsRed) (CFP/YFP-CRS-DsRed). (spie.org)
  • Human Caspase 9 recombinant protein catalytic subunits (NP_001220). (novusbio.com)
  • The CED-4-homologous protein FLASH is involved in Fas-mediated activation of caspase-8 during apoptosis [see comments] [published erratum appears in Nature 1999 Jul 1;400(6739):89]. (jax.org)
  • In this study, we investigated the function of p38 mitogen-activated protein kinase (MAPK) and caspase-8 in DATS-induced apoptosis of human CNE2 cells using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], flow cytometry assay, and Western blotting. (scielo.br)
  • On the basis of the superior killing by downstream caspase-1 and caspase-3, replication-deficient adenoviral vectors expressing conditional caspase-1 (Ad-G/iCasp1) or caspase-3 (Ad-G/iCasp3), regulated by nontoxic, lipid-permeable, chemical inducers of dimerization (CID), were constructed. (aacrjournals.org)
  • There is detectable activation of caspase-7 downstream, but not 3. (protocol-online.org)
  • Boesen-de Cock, Tepper, de Vries, van Blitterswijk, Borst: Common regulation of apoptosis signaling induced by CD95 and the DNA-damaging stimuli etoposide and gamma-radiation downstream from caspase-8 activation. (antibodies-online.com)
  • I am interested in the SiRNA for Human Caspase-8. (abcam.com)
  • This peptide corresponds to 16 amino acids near the center of human Caspase-9.PEP-0029 can be used as a blocking peptide with polyclonal antibody PA5-19903. (fishersci.com)
  • In cancer, therefore, one would anticipate caspases to be frequently rendered inactive, either by gene silencing or by somatic mutations. (mdpi.com)
  • This signal-induced endoproteolysis requires the activity of several gene products, including the IκB kinase complex and the caspase Dredd. (pnas.org)
  • Unexpectedly, a role for a caspase in Relish activation was indicated by the fact that mutants in Dredd , a Drosophila caspase gene, are deficient in Relish processing and antimicrobial peptide production ( 10 - 12 ). (pnas.org)
  • We have expressed the putative caspase‐like gene MaOC 1 from the toxic bloom‐forming cyanobacterium M icrocystis aeruginosa PCC 7806 in E scherichia coli . (ingentaconnect.com)
  • In this study, we evaluated the safety and efficacy of a novel suicide gene therapy that could potentially spare normal tissue while bypassing molecular mechanisms of apoptosis resistance by using chemically inducible effector caspases to trigger apoptosis in prostate cancer cells. (aacrjournals.org)
  • These results demonstrate that CID-regulated, caspase-based suicide gene therapy is safe and can inhibit the growth of experimental prostate cancer in vitro and in vivo through potent induction of apoptosis, providing a rationale for further development. (aacrjournals.org)
  • Feng Q, Li P, Leung PC, Auersperg N: Caspase-1zeta, a new splice variant of the caspase-1 gene. (drugbank.ca)
  • In this study, we report the establishment of conditional knockout of the caspase-8 gene using the Cre/ loxP recombination system, and its use for exploring these other functions. (jimmunol.org)
  • 103 Caspase 12 (Gene/pseudogene) (CASP12) Antikörper von 21 Herstellern verfügbar auf www.antikoerper-online.de. (antikoerper-online.de)
  • Caspase 2 was initially identified as a neuronally expressed developmentally down-regulated gene (HUGO gene nomenclature CASP2) and has been shown to be required for neuronal death induced by several stimuli, including NGF (nerve growth factor) deprivation and Aβ (β-amyloid). (sigmaaldrich.com)
  • Mutations in the caspase-8 gene not only affect apoptosis but also affect host defense. (aappublications.org)
  • Immunohistochemical analysis of frozen H1650 xenograft section, using Cleaved Caspase-3 (Asp175) Antibody #9661 . (cellsignal.com)
  • Company 1 cleaved caspase-3 rabbit polyclonal antibody shows high background and does not detect distinct bands in the expected 19/17 kDa range. (cellsignal.com)
  • Company 2 active caspase-3 rabbit polyclonal antibody detects multiple non-specific bands at various molecular weights but weakly detects the bands of interest in the 19/17 kDa and 12 kDa range. (cellsignal.com)
  • Company 1 active caspase-3 rabbit monoclonal antibody detects multiple non specific bands at various molecular weights. (cellsignal.com)
  • The antibody recognizes only the 17 kDa band corresponding to one form of the large fragment of cleaved caspase-3. (cellsignal.com)
  • The specimens were labelled immunohistochemically for binding of an anti-caspase 9 primary antibody. (biomedsearch.com)
  • The following antibody was used in this experiment: Caspase 12 Polyclonal Antibody from Thermo Fisher Scientific, catalog # PA5-19963, RRID AB_11153731. (thermofisher.com)
  • Immunohistochemistry-Paraffin: Caspase-9 Antibody [NB100-56118] - Analysis Human Brain sections stained for cleaved Caspase-9 expression using this antibody at 1:2000. (novusbio.com)
  • Immunohistochemistry-Paraffin: Caspase-9 Antibody [NB100-56118] - Analysis of Capase-9 in mouse transplanted lung tumor section using anti-Caspase-9 antibody. (novusbio.com)
  • This antibody detects both the pro- and active-Caspase 9 forms. (novusbio.com)
  • Only low levels of active Caspase-3 appear to be required, helping explain why its critical role has been obscured in prior studies. (jneurosci.org)
  • An active caspase consists of two large and two small subunits that form two heterodimers which associate in a tetramer. (bio-medicine.org)
  • Caspase-9 staining in the nucleus is considered to be an indication of active Caspase-9. (novusbio.com)
  • Fluorescence detection is highly sensitive and can be used to measure even very small amounts of active caspase. (clontech.com)
  • To investigate the requirement for the PIDDosome in caspase-2-dependent neuronal death, we have examined the necessity for each component in induction of active caspase 2 and in execution of caspase-2-dependent neuronal death. (sigmaaldrich.com)
  • We find that both NGF deprivation and Aβ treatment of neurons induce active caspase 2 and that induction of this activity depends on expression of RAIDD, but is independent of PIDD expression. (sigmaaldrich.com)
  • Apoptosis is a physiological mechanism of homeostasis and development, and caspases are the executioners of apoptosis. (biomedsearch.com)
  • Note that in addition to apoptosis, Caspase-8 is also required for the inhibition of another form of programmed cell death called Necroptosis . (wikipedia.org)
  • Injection of LPS into the substantia nigra of rats increased caspase-8 and caspase-3 activity, and pharmacological inhibition of caspase-3/7 prevented production of cytokines and proinflammatory molecules in response to LPS. (sciencemag.org)
  • Injection of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces pathophysiology that resembles Parkinson's disease, and pharmacological inhibition of caspase-8 conferred a modest degree of protection against MPTP-induced neuronal death. (sciencemag.org)
  • In particular, it has been shown that NO synthase (NOS) activity can lead to caspase inhibition by a mechanism independent of cyclic guanosine monophosphate, that caspases can be S-nitrosylated by NO donors in cellular and in vitro systems, that the S-nitrosylation takes place solely on the active-site cysteine, and that this modification inhibits caspase activity in a reversible manner ( 2-4 ). (sciencemag.org)
  • Systemic treatment of zebrafish or local treatment of the chick chorioallantoic membrane with ScA resulted in dose-dependent inhibition of angiogenesis, whereas topical treatment blocked tumor growth among caspase-8-expressing tumors. (pnas.org)
  • The results demonstrate that considering allosteric inhibition of caspase 3 as a shift between discrete 'off-state' or 'on-state' conformations is insufficient. (rcsb.org)
  • Inhibition of JNK1/2 by specific inhibitors significantly abolished the TAIII-induced activation of the caspase-8. (springer.com)
  • This Review gives an overview of caspases and their classification, structure, and substrate specificity. (jci.org)
  • DFFA is the substrate for caspase-3 and triggers DNA fragmentation during apoptosis. (wikipedia.org)
  • Caspase enzymes specifically recognize a 4 or 5 amino acid sequence on the target substrate which necessarily includes an aspartic acid residue. (bio-medicine.org)
  • The binding of extracellular ligands to death receptors triggers the formation of a DISC complex resulting in the activation of initiator caspases 8 and/or 10. (els.net)
  • Furthermore, TCDD was able to trigger BHV-1-induced apoptosis by up-regulating the activation of initiator caspases 8 and 9, as well as of effector caspase 3. (curehunter.com)
  • Caspases are synthesised as inactive zymogens (pro-caspases) that are only activated following an appropriate stimulus. (wikipedia.org)
  • All caspases are produced as catalytically inactive zymogens or proenzymes containing a prodomain, a large (p20) and a small subunit (p10). (els.net)
  • To keep the cells from self-destructing, caspases are kept in an inactive state. (wisegeek.com)
  • The active initiator caspases cleave the inactive effector caspases, which then activate apoptosis. (wisegeek.com)
  • A more comprehensive view of allosteric regulation of caspase 3 requires the representation of an ensemble of inactive states and shows that subtle structural changes lead to the population of the inactive ensemble. (rcsb.org)
  • A, Caspases are synthesized as inactive pro-enzymes with an N-terminal prodomain and a large and small subunit of 17 to 21 and 10 to 13 kD, respectively. (plantphysiol.org)
  • Caspases are synthesized as inactive proenzymes comprising an N-terminal peptide (prodomain) together with one large and one small subunit. (portlandpress.com)
  • 2. Caspase antibodies are classical tools for detecting inactive (pro) and active (cleaved) forms of the enzymes. (novusbio.com)
  • Caspase-8 can activate caspase-3/7, and LPS treatment increased caspase-8 activity in BV2 cells, which required Toll-like receptor 4 (TLR4, a receptor that recognizes LPS). (sciencemag.org)
  • A hierarchy of caspase activation exists whereby initiator caspases become activated to cleave and activate effector caspases. (els.net)
  • There are two major classes of caspase activity that activate apoptosis. (wisegeek.com)
  • Once activated, the initiator caspases can activate other caspases such as the EFFECTOR CASPASES. (curehunter.com)
  • I need to activate caspase-1 to trigger inflammation and pyroptotic cell death. (protocol-online.org)
  • Additionally, effector caspase activity can cause the nuclear DNA to fragment. (wisegeek.com)
  • Similar to Caspase 3 , Caspase-7 is an effector caspase and plays a key role in apoptotic execution. (novusbio.com)
  • gondii significantly reduced Fas/CD95-triggered apoptosis in HeLa cells by inhibiting the activities of initiator caspases 8 and 9 and effector caspase 3/7. (curehunter.com)
  • FasL expression was up-regulated by taiwanin A at both the transcriptional and translational levels, following the activation of caspase initiator caspase-10 and effector caspase-7. (thefreedictionary.com)
  • On www.antibodies-online.com are 474 Caspase 9, Apoptosis-Related Cysteine Peptidase (CASP9) Antibodies from 35 different suppliers available. (antibodies-online.com)
  • Antibodies to p38, phospho-p38 (p-p38), and caspase-8 were purchased from Cell Signaling (USA). (scielo.br)
  • The value of the caspase market is hard to establish, since while central to many mechanisms of actions for many drugs, these drugs act slightly further upstream, modulating the relative activity of caspase molecules, but it is clear that they offer significant potential for R&D in pharma! (bioportfolio.com)
  • However, we find at a biochemical level that Caspase-6 is activated effectively only by Caspase-3 but not other "upstream" caspases, prompting us to revisit the role of Caspase-3. (jneurosci.org)
  • Caspases also have a role in inflammation, whereby it directly processes pro-inflammatory cytokines such as pro-IL1β. (wikipedia.org)
  • [5] Caspases involved with processing inflammatory signals are also implicated in disease. (wikipedia.org)
  • Depending on the structure of the prodomain and their function, caspases are typically divided into 3 major groups (Figure 1 A). The caspases with large prodomains are referred to as inflammatory caspases (group I) and initiator of apoptosis caspases (group II), while caspases with a short prodomain of 20-30 amino acids are named effector caspases (group III). (jci.org)
  • Caspase-1 as a multifunctional inflammatory mediator: noncytokine maturation roles. (nih.gov)
  • Thus, caspase activation in microglia does not trigger cell death, but rather mediates microglial activation and inflammatory responses. (sciencemag.org)
  • The pro-domain of the intrinsic initiator caspases and the inflammatory caspases contains a single death fold known as caspase recruitment domain (CARD), while the pro-domain of the extrinsic initiator caspases contains two death folds known as death effector domains (DED). (wikipedia.org)
  • Apoptosis is ultimately carried out by the sequential activation of initiator and executioner caspases, which constitute a family of intracellular proteases involved in dismantling the cell in an ordered fashion. (mdpi.com)
  • Executioner caspases have only rarely been found mutated or silenced, and also initiator caspases are only affected in particular types of cancer. (mdpi.com)
  • There are two types of caspases: initiator caspases that are activated by dimerization, and executioner caspases that are cleaved by initiator caspases. (biolegend.com)
  • This involves a number of mitochondria-associated factors like BID and cytochrome C, and eventually results in the dimerization of caspase-9 and the subsequent activation of the executioner caspases. (biolegend.com)
  • Caspases are responsible for the deliberate disassembly of the cell into apoptotic bodies during apoptosis. (biovision.com)
  • Caspases have other identified roles in programmed cell death such as pyroptosis and necroptosis . (wikipedia.org)
  • [5] Conversely, over-activation of some caspases such as caspase -3 can lead to excessive programmed cell death. (wikipedia.org)
  • Most caspases play a role in programmed cell death. (wikipedia.org)
  • Caspase activity is due to a group of very complex enzymes that regulate programmed cell death, or apoptosis , in multicellular organisms. (wisegeek.com)
  • Caspase-3 activation and function have been well-defined during programmed cell death, but caspase activity, at low levels, is also required for developmental processes such as lymphoid proliferation and erythroid differentiation. (rcsb.org)
  • Axon degeneration initiated by trophic factor withdrawal shares many features with programmed cell death, but many prior studies discounted a role for caspases in this process, particularly Caspase-3. (jneurosci.org)
  • Caspases: key players in programmed cell death. (anaspec.com)
  • Caspase-1-dependent programmed cell death (known as pyroptosis) is a unique form of cell death that does not depend on the activation of caspase-3. (protocol-online.org)
  • Like other caspases it also plays a role in apoptosis (programmed cell death), but only when over-expressed. (sciencephoto.com)
  • Caspase 9 is active as a heterotetramer, is present in the cytosol and, upon activation, translocates to the mitochondria. (fishersci.com)
  • Both pro and active/cleaved Caspase-9 staining may also be seen in the mitochondria. (novusbio.com)
  • In comparison with an electron microscopic assessment of the abnormalities seen in endplate myopathy, we found that activated caspases were present at between 15 and 57% of endplates, similar to the proportion of endplates with degenerating mitochondria or vacuoles. (sigmaaldrich.com)
  • Once active, initiator caspases proteolytically cleave effector caspases at distinct aspartate residues, to release the prodomain, large and small subunits. (els.net)
  • The presence of the large or small subunits in western blots is considered to be a marker of caspase activation. (novusbio.com)
  • Although caspase-1 has no obvious role in cell death, it has become the first identified member of a large family of proteases whose members have distinct roles in inflammation and apoptosis ( Fig. 1 A). In apoptosis, caspases function in both cell disassembly (effectors) and in initiating this disassembly in response to proapoptotic signals (initiators). (sciencemag.org)
  • The caspases are a family of cytosolic proteases with essential roles in inflammation and apoptosis. (nature.com)
  • The mammalian caspases play distinct roles in apoptosis and inflammation. (bio-medicine.org)
  • The effector caspases inhibit the enzymes that repair damaged DNA. (wisegeek.com)
  • We provide a huge selection of cytokines and growth factors as well as many different enzymes such as caspases and kinases. (promocell.com)
  • We show that, within the modified loop, Ser 150 evolved with the apoptotic caspases, whereas Thr 152 is a more recent evolutionary event in mammalian caspase-3. (rcsb.org)
  • Schematic representation of structural features of mammalian caspases. (plantphysiol.org)
  • Thus, in contrast to the more widespread neuroprotective actions of sex steroids in the mammalian nervous system, in the AVPV estrogen regulates dopaminergic neuron number through a caspase-dependent mechanism of apoptotic cell death. (jneurosci.org)
  • In mammalian cells, several pro-apoptotic proteases called caspases were found to play a crucial role in ER stress-induced PCD. (frontiersin.org)
  • Decreased caspase-3 S-nitrosylation was associated with an increase in intracellular caspase activity. (sciencemag.org)
  • Caspase activity in microglia does not trigger cell death, but rather induces proinflammatory responses. (sciencemag.org)
  • ScA Induces Apoptosis Selectively via Caspase 8. (pnas.org)
  • PML induces a novel caspase-independent death process. (biomedsearch.com)
  • We show that treatment of wild-type or PIDD-null neurons with Aβ or NGF deprivation induces formation of a complex of caspase 2 and RAIDD. (sigmaaldrich.com)
  • Some activating multiprotein complexes includes: The death-inducing signaling complex (DISC) during extrinsic apoptosis The apoptosome during intrinsic apoptosis The inflammasome during pyroptosis Once appropriately dimerised, the Caspases cleave at inter domain linker regions, forming a large and small subunit. (wikipedia.org)
  • Caspase-12 is activated by ER stress, including disruption of ER calcium homeostasis, and mediates ER stress-induced apoptosis. (thermofisher.com)
  • Caspase-12 mediates cytotoxicity induced by amyloid-beta. (thermofisher.com)
  • Thus, besides participating in cell death induction by receptors of the TNF/nerve growth factor family, caspase-8, apparently independently of these receptors, also mediates nonapoptotic and perhaps even antiapoptotic activities. (jimmunol.org)
  • Mutations in Caspase 9 affect brain development. (fishersci.com)
  • Caspase-8 mutations lead to a disorder characterized by expansion of lymphocytes in secondary lymphoid organs and abnormal lymphocyte activation. (aappublications.org)
  • Involved in the activation cascade of caspases responsible for apoptosis execution. (abcam.com)
  • Further, Caspase 9 is involved in the activation cascade of caspases responsible for apoptosis execution. (fishersci.com)
  • The large and small subunit associate with each other to form an active heterodimer caspase. (wikipedia.org)
  • Caspases, a family of c ysteinyl a spartate- s pecific p rote ases , are synthesized as zymogens with a prodomain of variable length followed by a large subunit (p20) and a small subunit (p10). (jci.org)
  • In western blots, the proform of caspase-9 is detected at ~50 kDa, the large subunit at ~35 kDa, and the small subunit at ~15 kDa. (novusbio.com)
  • The most common caspase assays come in kits and use fluorometric, colorimetric, or flow cytometry-based methods. (biocompare.com)
  • To assess whether the observed apoptosis was caspase-dependent or -independent, assays measuring caspase 3 activity and apoptosis-inducing factor (AIF) labeling were performed. (bioone.org)
  • The Caspase-3 Fluorescent Assays detect the shift in fluorescence emission of 7-amino-4-trifluoromethyl coumarin (AFC). (clontech.com)
  • We offer caspase detection assays in two formats: assay kits and 96-well plates. (clontech.com)
  • Using phage display to discover molecules that bind the zymogen, we report the identification of a peptide that specifically impairs the function of caspase-6 in vitro and in neuronal cells. (nature.com)
  • Your search returned 768 Apoptosis Caspase Assay Cell Viability and Proliferation across 19 suppliers. (biocompare.com)
  • After human CNE2 cells were treated with 100 μM DATS and inhibitors (10 μM SB203580 and Z-LETD-FMK for p38MAPK and caspase-8, respectively), changes in cell viability and apoptosis and in p38MAPK and caspase-8 activity were detected. (scielo.br)
  • As of 2009, there are 11 or 12 confirmed caspases in humans [note 1] and 10 in mice, carrying out a variety of cellular functions. (wikipedia.org)
  • Activation of Caspases ensures that the cellular components are degraded in a controlled manner, carrying out cell death with minimal effect on surrounding tissues . (wikipedia.org)
  • Caspases target multiple aspects of the cellular architecture to induce collapse of organelles and the cytoskeleton. (els.net)
  • Signalling networks that regulate cellular processes critical for cell survival are inactivated by caspases. (els.net)
  • Second, in tumor cells caspases might be kept in check by cellular caspase inhibitors such as c-FLIP or XIAP. (mdpi.com)
  • These findings provide the first evidence supporting the view that caspase activation in human disease can play a prominent role in localized cellular degenerative processes without causing nuclear or cell death. (sigmaaldrich.com)
  • We also describe the current knowledge of how interference with caspase signaling can be used to pharmacologically manipulate cell death. (jci.org)
  • Our results show that insulin deprivation decreases caspase-dependent apoptotic signaling in cultured rat SCs evidencing a possible mechanism by which lack of insulin can affect spermatogenesis and fertility. (hindawi.com)
  • If apoptotic signaling molecules reach the cytosol, they can recruit caspase-9 [ 18 , 19 ]. (hindawi.com)
  • Because no such phenotype results from targeting of any of the known TNF/NGF family members that use caspase-8 in their signaling, these findings suggested that caspase-8 serves other functional roles as well. (jimmunol.org)
  • 8 and Caspase 9 colorimetric assay: R&D Systems, Inc. (thefreedictionary.com)
  • The influence of compound 3 on caspase 3/7, caspase 8 and caspase 9 activity in CCRF-CEM leukemia cells was detected using Caspase-Glo 3/7, Caspase-Glo 8 and Caspase-Glo 9 Assay kits (Promega, Germany). (thefreedictionary.com)
  • The influence of compounds 2-4 on caspase 3/7, caspase 8 and caspase 9 activity in CCRF-CEM leukemia cells was detected using Caspase-Glo 3/7, Caspase-Glo 8 and Caspase-Glo 9 Assay kits (Promega, Germany). (thefreedictionary.com)
  • The Caspase-9/6 Fluorescent Assay detects the shift in fluorescence of 7- amino-4-methoxy coumarin (AMC). (clontech.com)
  • The ApoAlert Caspase Profiling Assay Plate can be used to simultaneously analyze several different caspases in your sample, with up to 24 wells available for each caspase. (clontech.com)
  • In the same way caspases are activated, many anti-apoptotic molecules can also inhibit caspases to prevent cell death, by a similar mechanism of structural alteration. (bioportfolio.com)
  • Recently, Caspase-6 was implicated based on pharmacological and knockdown evidence, and we report here that genetic deletion of Caspase-6 indeed provides partial protection from degeneration. (jneurosci.org)
  • A ) Caspases have been found in organisms ranging from C. elegans to humans. (sciencemag.org)
  • In humans, dysfunctional Caspase 9 expression vary from tissue to tissue. (fishersci.com)
  • Upon vector transduction followed by CID administration, aggregation and activation of these recombinant caspases occur, leading to rapid apoptosis. (aacrjournals.org)