Caspases
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.
Caspase Inhibitors
Apoptosis
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Caspase 6
Caspase 3
Caspase 7
Amino Acid Chloromethyl Ketones
Cysteine Proteinase Inhibitors
Caspase 9
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.
Caspases, Effector
Caspase 8
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.
Caspase 2
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.
Caspases, Initiator
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.
Enzyme Activation
X-Linked Inhibitor of Apoptosis Protein
DNA Fragmentation
Cytochrome c Group
Proto-Oncogene Proteins c-bcl-2
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.
Inhibitor of Apoptosis Proteins
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.
Caspase 1
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.
Antigens, CD95
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.
Mitochondria
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)
Cysteine Endopeptidases
Apoptotic Protease-Activating Factor 1
Poly(ADP-ribose) Polymerases
Cytochromes c
Jurkat Cells
Cell Death
Caspase 10
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.
bcl-2-Associated X Protein
BH3 Interacting Domain Death Agonist Protein
Apoptosis Regulatory Proteins
Signal Transduction
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.
bcl-X Protein
Apoptosomes
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.
Apoptosis Inducing Factor
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.
Staurosporine
In Situ Nick-End Labeling
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.
Calpain
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.
Fas-Associated Death Domain Protein
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.
Enzyme Inhibitors
Fas Ligand Protein
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.
Cell Survival
Tumor Cells, Cultured
Caspase 12
Serpins
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.
HL-60 Cells
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)
Annexin A5
TNF-Related Apoptosis-Inducing Ligand
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.
Necrosis
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.
Proteins
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.
Carrier Proteins
Membrane Potential, Mitochondrial
HeLa Cells
Blotting, Western
Substrate Specificity
Cells, Cultured
Mitochondrial Proteins
Granzymes
Amino Acid Sequence
Cascara
Tumor Necrosis Factor-alpha
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.
Etoposide
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.
CRADD Signaling Adaptor Protein
bcl-2 Homologous Antagonist-Killer Protein
Molecular Sequence Data
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.
Caspase 14
Reactive Oxygen Species
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.
Transfection
Genes, bcl-2
Cytosol
Phosphatidylserines
Models, Biological
Receptor-Interacting Protein Serine-Threonine Kinases
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.
Death Domain Receptor Signaling Adaptor Proteins
Mitochondrial Membranes
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).
Lamins
Tumor Suppressor Protein p53
Dose-Response Relationship, Drug
Drosophila Proteins
Coumarins
U937 Cells
Intracellular Signaling Peptides and Proteins
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.
Flow Cytometry
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.
Proto-Oncogene Proteins
Protein Processing, Post-Translational
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.
Protein Structure, Tertiary
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.
Antineoplastic Agents, Phytogenic
JNK Mitogen-Activated Protein Kinases
Receptors, TNF-Related Apoptosis-Inducing Ligand
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.
Receptors, Death Domain
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.
Receptors, Tumor Necrosis Factor
NF-kappa B
Adaptor Proteins, Signal Transducing
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
Tosyllysine Chloromethyl Ketone
Neoplasm Proteins
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.
Protein Synthesis Inhibitors
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.
CASP8 and FADD-Like Apoptosis Regulating Protein
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.
Bongkrekic Acid
Serine Endopeptidases
bcl-Associated Death Protein
Proteolysis
Membrane Potentials
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).
Propidium
Intracellular Membranes
Cell Nucleus
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, Fluorescence
Neurons
Proteasome Endopeptidase Complex
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.
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)
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Some reports stage to a essential position of caspases for
DCP-315P Testengine - DCP-315P Fragen&Antworten, DCP-315P Trainingsunterlagen - Istatistikselenvanterkontrolu
Cloning and expression of rat caspase-6 and its localization in renal ischemia/reperfusion injury<...
Role of Tyrosine Kinase Lyn and Cleaved Form by Caspases in Psoriasis - Full Text View - ClinicalTrials.gov
IAP1-Mediated Ubiquitylation Controls Activation of the Initiator Caspase DRONC Independent of Protein Degradation | proLékaře...
β-Phenylethyl isothiocyanate mediated apoptosis; Contribution of Bax and the mitochondrial death pathway | [email protected]
Caspase 12 - Wikipedia
Caspase-mediated cleavage of the stacking protein GRASP65 is required for Golgi fragmentation during apoptosis. - Oxford...
Caspase-3-Generated Fragment of Gelsolin: Effector of Morphological Change in Apoptosis | Science
NIOSHTIC-2 Publications Search - 20044754 - S-nitrosylation of FLICE inhibitory protein determines its interaction with RIP1...
Death receptor 6 induces apoptosis not through type I or type II pathways, but via a unique mitochondria-dependent pathway by...
KEGG PATHWAY: Apoptosis - Homo sapiens (human)
KEGG PATHWAY: Apoptosis - Bos taurus (cow)
KEGG PATHWAY: Apoptosis - Homo sapiens (human)
Mécanismes dactivation, de régulation et de lactivité des caspases - Project - Fonds Santé
Pathogen blockade of TAK1 triggers caspase-8-dependent cleavage of gasdermin D and cell death | Science
SMART: CASc domain annotation
Reversibility of apoptosis in cancer cells<...
Apoptogenic factors released from mitochondria
Executor Checklist - Catherine Barrie, CGA, CPA, MBA
Processing by Caspases | Science Signaling
Apoptosis - Wikipédia Sunda, énsiklopédi bébas
Caspases determine the vulnerability of oligodendrocytes in the ischemic brain<...
Plus it
Caspase 3 - Wikipedia
Caspase-7 was regarded as redundant with caspase-3 because these related cystein - How NF-B is activated: the role of the IB...
Plus it
Structure Based Study of CA SPASE-3 and D-Arginine Dehydrogenase by Guoxing Fu
AID 666968 - Inhibition of human recombinant caspase-3 catalytic domain using Ac-DEVD-pNA as substrate at 20 ug/ml preincubated...
Proapoptotic Effects of Caspase-1/Interleukin-Converting Enzyme Dominate in Myocardial Ischemia | Circulation Research
Oncotic necrosis and caspase-dependent apoptosis during galactosamine- by Jaspreet S. Gujral, Anwar Farhood et al.
The role of caspases in development, immunity, and apoptotic signal transduction: lessons from knockout mice. - PubMed - NCBI
Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity | Protocol (Translated to Swedish)
Regulation of caspase-3 processing by cIAP2 controls the switch between pro-inflammatory activation and cell death in microglia.
Activation of caspase-2 mediates the apoptosis induced by GTP-depletion in insulin-secreting (HIT-T15) cells
Caspases, bax e bak , MOMP
Jiahuai Han: Aflame on inflammation and p38 | JCB
Casticin induces caspase-mediated apoptosis via activation of mitochondrial pathway and upregulation of DR5 in human lung...
Can the NucView® caspase-3 substrates be used on (PFA or methanol) fixed cells or tissue cryosections? | Biotium
VX-950 - Role for Caspase-Mediated Cleavage of Rad51 in Induction of Apoptosis
Supplementary MaterialsDataSheet 1 - Role for Caspase-Mediated Cleavage of Rad51 in Induction of Apoptosis
Taking DRACOnian measures against viruses
Apoptosis (Homo sapiens) - WikiPathways
Apoptosis (Homo sapiens) - WikiPathways
In Situ Pan-Caspase Assay Kit from CHEMICON
Caspase 2 (CASP2) ELISA Kit
Caspase 8
Caspase-8 is a caspase protein, encoded by the CASP8 gene. It most likely acts upon caspase-3. CASP8 orthologs[5] have been ... Apoptosis & Caspase 8-The Proteolysis Map (animation). *Caspase 8 at the US National Library of Medicine Medical Subject ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... 1f9e: CASPASE-8 SPECIFICITY PROBED AT SUBSITE S4: CRYSTAL STRUCTURE OF THE CASPASE-8-Z-DEVD-CHO ...
Apoptosis
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. ...
Bcl-2 family
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 ...
GSDMD
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, ...
Autoimmune lymphoproliferative syndrome
Fas and Fas-ligand interact to trigger the caspase cascade, leading to cell apoptosis. Patients with ALPS have a defect in this ... CEDS: Caspase 8 deficiency state. No longer considered a subtype of ALPS but distinct disorder ...
CAPN2
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". ...
GZMB
Cohen GM (1997). "Caspases: the executioners of apoptosis". Biochem. J. 326 (1): 1-16. doi:10.1042/bj3260001. PMC 1218630. PMID ...
Ablation
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 ...
S. Murty Srinivasula
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 ...
Hypersensitive response
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. ...
Phycocyanin
Caspases are part of the apoptosis pathway. When BCl-2 decreases, the expression of caspases increases. As a result, apoptosis ...
Programmed cell death
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 ...
Cell death
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 ...
Vishva Dixit
... 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 ...
NLRP10
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, ...
Chromosome 16
CASP16P: encoding protein Caspase 16, pseudogene. *CCDC113: encoding protein Coiled-coil domain-containing protein 113 ...
RNA silencing
Caspase 2 Ocular and retinal disorders. AGN211745. Age-related macular degeneration, choroidal neovascularization. VEGFR1 ...
Pattern hair loss
Hair follicles in anaphase express four different caspases. Significant levels of inflammatory infiltrate have been found in ...
BUB1
Kitagawa K, Niikura Y (Apr 2008). "Caspase-independent mitotic death (CIMD)". Cell Cycle. 7 (8): 1001-5. doi:10.4161/cc.7.8. ...
Neurodegeneration
There are two types of caspases: initiators and effectors. Initiator caspases cleave inactive forms of effector caspases. This ... Pharmacological approaches involve inhibitors of caspase activity, and caspase inhibition might delay cell death in the ... 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. ...
Pardaxin
... 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 ...
Pyroptosis
... 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- ...
FADD
... 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 ...
William C. Earnshaw
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 ...
Phytaspase
... 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 ...
Death effector domain
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 ...
Nerve tissue protein
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 ...
XIAP
... 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 ...
Caspase - Wikipedia
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 regulators
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. ...
JCI -
Caspases: pharmacological manipulation
of cell death
... 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 ...
Caspase-3 (P42574) | InterPro | EMBL-EBI
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 [Mus musculus] - Protein - NCBI
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. ...
"Caspase-3" and docking - PubMed - NCBI
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 ...
Activated by Caspases | Science Signaling
... 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 ...
Activated by Caspases | Science Signaling
Caspase 10 - Wikipedia
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 ...
Caspases: Enemies Within | Science
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 ...
Caspase-activated DNase - Wikipedia
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 ...
Caspase Pathways
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 ...
Caspases - MP Biomedicals
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.. ...
Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory disease | Nature
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 ...
Caspase-Glo® 8 Assay, 10ml
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 ...
Fas-Induced Caspase Denitrosylation | Science
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 ...
Dismantling the Apoptotic Cell by Caspases
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 ...
Apoptosis and caspases regulate death and inflammation in sepsis
TauC3 (Transgenic caspase-cleaved tau) | ALZFORUM
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 ...
Caspase 8: igniting the death machine
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 ...
What is Caspase Activity? (with pictures)
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. ...
Caspase Assay | Biocompare.com
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 ...
Cancers | Free Full-Text | The Enigmatic Roles of Caspases in Tumor Development
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 ...
Caspase-mediated processing of the Drosophila NF-κB factor Relish | PNAS
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 marine lipopeptide somocystinamide A triggers apoptosis via caspase 8 | PNAS
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 ...
RCSB PDB - 6BFL: Caspase-3 Mutant- D9A,D28A,T245D
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. A. 175. Homo sapiens. Mutation(s): 2 Gene Names: CASP3, CPP32. EC: 3.4.22.56. ... Caspase-3. B. 102. Homo sapiens. Mutation(s): 1 Gene Names: CASP3, CPP32. EC: 3.4.22.56. ...
RCSB PDB - 6BDV: Crystal structure of Caspase 3 S150A
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. ...
Orthocaspases are proteolytically active prokaryotic caspase homo...: Ingenta Connect
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 ...
Allosteric peptides bind a caspase zymogen and mediate caspase tetramerization | Nature Chemical Biology
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 ...
CleavageInitiatorFamily of cysteineProteinsPathwaysInhibitorProteasePathwayActivatesProteolyticSubstratesDownstreamEnzymeProteinHuman caspaseSubstrateGeneActive caspaseExecutioners of apoptosisActivateAntibodyEffector caspaseInhibitionInactiveUpstreamDisassembly of the cellMitochondriaSubunitsAntibodiesNeuronalInflammationInhibitEnzymesMammalianInflammatoryCellIntracellularInducesIntrinsicHumansMediatesMutationsResponsible for apoptosis executionSmall subunitCellularSignalingPharmacologicalRecombinantColorimetric
Cleavage53
- Activation involves dimerization and often oligomerisation of pro-caspases, followed by cleavage into a small subunit and large subunit. (wikipedia.org)
- CAD release from ICAD inhibition is achieved by cleavage of ICAD at these Asp residues by the caspase-3. (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)
- 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)
- 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)
Initiator31
- 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)
- 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)
- 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)
- A hierarchy of caspase activation exists whereby initiator caspases become activated to cleave and activate effector caspases. (els.net)
- The prodomain of the initiator (also known as apical) caspases (2, 8, 9 and 10) is much longer than that of effector caspases 3, 6 and 7. (els.net)
- Once active, initiator caspases proteolytically cleave effector caspases at distinct aspartate residues, to release the prodomain, large and small subunits. (els.net)
- Cytoplasmic cytochrome c drives the formation of the apoptosome and activation of initiator caspase 9. (els.net)
- 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)
- Two papers in the September issue of Structure with Folding & Design have for the first time revealed the structure of the key apoptotic initiator, caspase 8. (nih.gov)
- The first are initiator caspases, which are regulated by inhibitors. (wisegeek.com)
- The active initiator caspases cleave the inactive effector caspases, which then activate apoptosis. (wisegeek.com)
- 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 is experimental evidence from transgenic mice that certain initiator caspases, such as caspase-8 and -2, might act as tumor suppressors. (mdpi.com)
- Loss of the initiator caspase of the intrinsic apoptotic pathway, caspase-9, however, did not promote cellular transformation. (mdpi.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)
- Initiator caspases may be activated by autoprocessing when clustering occurs e.g. at the cytosolic part of (activated) cell death receptors. (plantphysiol.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)
- Caspase-9 is involved in mitochondrial apoptosis pathway and is an initiator caspase. (novusbio.com)
- Once activated, the initiator caspases can activate other caspases such as the EFFECTOR CASPASES. (curehunter.com)
- 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)
- 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)
- There are two types of caspases: initiator caspases that are activated by dimerization, and executioner caspases that are cleaved by initiator caspases. (biolegend.com)
- 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)
- Together with caspase-10 it belongs to the so-called initiator caspase group, and is important effector activation competent. (thefreedictionary.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)
- 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)
- Activation of caspase-9, a key event in stress-mediated apoptosis, also has been shown to be an initiator caspase. (spie.org)
- However, the timing or activation sequence of these initiator caspases, which trigger apoptotic pathway, is unclear. (spie.org)
- These data suggest parallel activation of initiator caspase-2 and caspase-9 in cisplatin-induced cell death. (spie.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)
Family of cysteine7
- 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)
Proteins17
- 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)
- 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)
- 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)
- 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)
Pathways15
- 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)
- Intense research into the signaling pathways of apoptosis has revealed a dominant role for proteases belonging to the caspase family, which in humans has 11 members at present. (nih.gov)
- 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)
Inhibitor12
- 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)
Protease17
- 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)
- 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 ( 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)
- 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)
Pathway11
- 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)
- 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)
- 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)
- 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)
- 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)
Activates7
- 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)
Proteolytic8
- 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)
- 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 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)
Substrates5
- 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)
- 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)
Downstream3
- 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)
Enzyme14
- 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)
- Structure of caspase-1 (CASP1), originally called interleukin-1 beta-converting enzyme (ICE), the first human caspase to be identified. (wikipedia.org)
- Caspase-10 is an enzyme that, in humans, is encoded by the CASP10 gene. (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)
Protein13
- 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)
- 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)
- 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)
Human caspase2
- 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)
Substrate3
- DFFA is the substrate for caspase-3 and triggers DNA fragmentation during apoptosis. (wikipedia.org)
- This Review gives an overview of caspases and their classification, structure, and substrate specificity. (jci.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)
Gene11
- 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)
Active caspase9
- 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)
- 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)
- This antibody detects both the pro- and active-Caspase 9 forms. (novusbio.com)
- 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)
Executioners of apoptosis1
- Apoptosis is a physiological mechanism of homeostasis and development, and caspases are the executioners of apoptosis. (biomedsearch.com)
Activate3
- 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)
- There are two major classes of caspase activity that activate apoptosis. (wisegeek.com)
- I need to activate caspase-1 to trigger inflammation and pyroptotic cell death. (protocol-online.org)
Antibody7
- 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)
- 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)
Effector caspase2
- 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)
Inhibition6
- 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)
- Inhibition of JNK1/2 by specific inhibitors significantly abolished the TAIII-induced activation of the caspase-8. (springer.com)
Inactive6
- 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)
- 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)
Upstream2
- 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)
Disassembly of the cell1
- Caspases are responsible for the deliberate disassembly of the cell into apoptotic bodies during apoptosis. (biovision.com)
Mitochondria4
- 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)
- 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)
Subunits1
- The presence of the large or small subunits in western blots is considered to be a marker of caspase activation. (novusbio.com)
Antibodies1
- On www.antibodies-online.com are 474 Caspase 9, Apoptosis-Related Cysteine Peptidase (CASP9) Antibodies from 35 different suppliers available. (antibodies-online.com)
Neuronal1
- 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)
Inflammation4
- Caspases also have a role in inflammation, whereby it directly processes pro-inflammatory cytokines such as pro-IL1β. (wikipedia.org)
- 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)
Inhibit2
- 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)
- The effector caspases inhibit the enzymes that repair damaged DNA. (wisegeek.com)
Enzymes2
- Caspase activity is due to a group of very complex enzymes that regulate programmed cell death, or apoptosis , in multicellular organisms. (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)
Mammalian4
- 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)
Inflammatory3
- Caspases involved with processing inflammatory signals are also implicated in disease. (wikipedia.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)
Cell51
- 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 have other identified roles in programmed cell death such as pyroptosis and necroptosis. (wikipedia.org)
- There are other identified roles of caspases such as cell proliferation, tumour suppression, cell differentiation, neural development and axon guidance and ageing. (wikipedia.org)
- Conversely, over-activation of some caspases such as caspase-3 can lead to excessive programmed cell death. (wikipedia.org)
- The integral role caspases play in cell death and disease has led to research on using caspases as a drug target. (wikipedia.org)
- Most caspases play a role in programmed cell death. (wikipedia.org)
- Caspase-14 plays a role in epithelial cell keratinocyte differentiation and can form an epidermal barrier that protects against dehydration and UVB radiation. (wikipedia.org)
- Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. (wikipedia.org)
- Caspase-3 is activated in the apoptotic cell. (wikipedia.org)
- Caspase-3 activation is a cell requirement during early stages of the skeletal myoblast differentiation. (wikipedia.org)
- Caspase signals resulting from the activation of nuclease CAD indicate that the cell differentiation is due to a CAD modification in chromatin structure. (wikipedia.org)
- We also describe the current knowledge of how interference with caspase signaling can be used to pharmacologically manipulate cell death. (jci.org)
- Caspases are serine proteases that are best characterized for their role as initiators and executioners of cell death, but LPS-treated cells did not appear to be undergoing cell death. (sciencemag.org)
- LPS treatment of BV2 cells triggered cell death in cocultured mouse dopaminergic MN9D cells, and fewer MN9D cells died when caspase-3 or caspase-7 was silenced in BV2 cells before LPS treatment. (sciencemag.org)
- Caspase activity in microglia does not trigger cell death, but rather induces proinflammatory responses. (sciencemag.org)
- In this review, we describe properties of caspases, how they kill a cell, how they are regulated, and discuss the potential therapeutic utility of caspase modulation. (sciencemag.org)
- For example, in drug-resistant forms of cancer, caspase-8 is in part responsible for making cells responsive to combination therapies such as eroltinib and cell-cycle inhibitiors. (bioportfolio.com)
- Further neurological implications include the caspase-3 dependent cell death in cerebellar granule neurons, which highlights potential neuro-toxicity of any caspase inhibiting compound. (bioportfolio.com)
- To address these issues, we immunoprecipitated caspase-3 from three different human B and T cell lines that express NOS ( Fig. 1 A) ( 5 ). (sciencemag.org)
- NOS and caspase-3 expression in human lymphocyte cell lines. (sciencemag.org)
- Signalling networks that regulate cellular processes critical for cell survival are inactivated by caspases. (els.net)
- Your search returned 768 Apoptosis Caspase Assay Cell Viability and Proliferation across 19 suppliers. (biocompare.com)
- Finally, caspase-independent cell death mechanisms might abrogate the selection pressure for caspase inactivation during tumor development. (mdpi.com)
- Moreover, experimental evidence suggests that caspases might play non-apoptotic roles in processes that are crucial for tumorigenesis, such as cell proliferation, migration, or invasion. (mdpi.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)
- In animal systems PCD is synonymous with apoptosis, a cell death process characterized by a distinct set of morphological and biochemical features, mediated by a class of specific Cys proteases called cysteinyl aspartate-specific proteinases (caspases). (plantphysiol.org)
- Although to date no functional homologs of animal caspases have been identified in plants, a vast amount of indirect evidence suggesting the existence in plants of true caspase-like activity and its functional involvement in plant cell death has accumulated. (plantphysiol.org)
- Caspase 8 initiates disassembly in response to extracellular apoptosis-inducing ligands and is activated in a complex associated with the cytoplasmic death domain of many cell surface receptors for the ligands. (biovision.com)
- The caspase 9 positive cell fraction was calculated for both epidermal and dermal cells in psoriatic lesions and healthy control skin. (biomedsearch.com)
- Although effective in preventing apoptosis, caspase inhibitors may lead to necrotic cell death, according to a report in The American Journal of Pathology . (medicalnewstoday.com)
- However, a new study published in The American Journal of Pathology raises serious safety concerns regarding the clinical use of caspase inhibitors by demonstrating the occurrence of delayed-onset necrotic, non-caspase-dependent liver cell injury. (medicalnewstoday.com)
- Our data suggest that one should be cautious in treating apoptotic cell death just with caspase inhibitors as, despite their efficacy in preventing apoptosis, these inhibitors may trigger necrotic cell death," noted Wen-Xing Ding, PhD, Associate Professor, Department of Pharmacology, Toxicology and Therapeutics of The University of Kansas Medical Center (Kansas City). (medicalnewstoday.com)
- Although blocking caspase protected against endotoxin-induced liver injury at an early time point (six hours), this protection was lost after 24 hours due to the switch of liver cell apoptosis to necrosis. (medicalnewstoday.com)
- Caspases: key players in programmed cell death. (anaspec.com)
- caspase-9 plays a central role in cell death through an array of apoptosis inducers-e.g. (thefreedictionary.com)
- In contrast to T47D cell lines, MCF7 cell lines with tiliroside of 50 [micro]g/ml occurred weak expression of Caspase 8 (Figure 6) moreover Caspase 9 was not expressed. (thefreedictionary.com)
- Cell death signals are transduced by death domain containing adapter molecules and members of the caspase family of proteases. (novusbio.com)
- Consistent with its role in cell death induction, deletion of caspase-8 in hepatocytes protected them from Fas-induced caspase activation and death. (jimmunol.org)
- Caspase-8 deletion in bone-marrow cells resulted in arrest of hemopoietic progenitor functioning, and in cells of the myelomonocytic lineage, its deletion led to arrest of differentiation into macrophages and to cell death. (jimmunol.org)
- 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)
- Studies of caspase-8 have focused on the ability of this caspase to interact with receptors of the TNF/nerve growth factor (NGF) 5 family and to signal for their cell death-inducing effect ( 10 , 11 , 12 ). (jimmunol.org)
- Induction of S phase cell arrest and caspase activation by polysaccharide peptide isolated from Coriolus versicolor enhanced the cell cycle dependent activity and apoptotic cell death of doxorubicin and etoposide, but not cytarabine in HL-60 cells. (greenmedinfo.com)
- Additionally, in caspase-1-dependent cell death the blebbing isn't the same as apoptosis and I only use the word blebbing because there is some level of membrane/cytoskeleton reorganization that occurs. (protocol-online.org)
- Caspase-1 is the only think I'm looking to be activated and that doesn't necessarily result in cell death. (protocol-online.org)
- Caspase-3 activation is almost the last step of cell death. (protocol-online.org)
- 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)
- Oftentimes, depending upon the specific cell type as well as the apoptotic stimuli used, one or more caspases will become activated. (clontech.com)
- Caspase profiling plates make it easy to profile caspase activities in a variety of cell lines after treatment with different apoptotic stimuli. (clontech.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)
- Like other caspases it also plays a role in apoptosis (programmed cell death), but only when over-expressed. (sciencephoto.com)
Intracellular1
- Decreased caspase-3 S-nitrosylation was associated with an increase in intracellular caspase activity. (sciencemag.org)
Induces3
- 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)
Intrinsic1
- 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)
Humans3
- As of 2009, there are 12 confirmed caspases in humans and 10 in mice, carrying out a variety of cellular functions. (wikipedia.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)
Mediates2
- 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)
Mutations2
- 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)
Responsible for apoptosis execution2
- 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)
Small subunit3
- 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)
Cellular2
Signaling3
- 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)
Pharmacological1
- 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)
Recombinant1
- Upon vector transduction followed by CID administration, aggregation and activation of these recombinant caspases occur, leading to rapid apoptosis. (aacrjournals.org)
Colorimetric2
- The most common caspase assays come in kits and use fluorometric, colorimetric, or flow cytometry-based methods. (biocompare.com)
- 8 and Caspase 9 colorimetric assay: R&D Systems, Inc. (thefreedictionary.com)