Substrate of caspase 8. Medical search. Frequent questions

This enzyme catalyses the following chemical reaction Strict requirement for Asp at position P1 and has a preferred cleavage sequence of Leu-Gln-Thr-Asp!Gly Caspase-10 is an initiator caspase, as are caspase-2 (EC 3.4.22.55), caspase-8 (EC 3.4.22.61) and caspase-9 (EC 3.4.22.62). (wikipedia.org)
Maluch I, Grzymska J, Snipas S, Salvesen GS , Drag M. Evaluation of the effects of phosphorylation of synthetic peptide substrates on their cleavage by caspase-3 and -7. (academictree.org)
Inflammasome-associated caspases mediate the proteolytic cleavage and activation of the Gasdermin D N-terminal domain ( GSDMD-NT ) [5]. (invivogen.com)
Caspases are a group of signaling proteins that have proteolytic function, and drive apoptosis through a chain of cleavage events. (biolegend.com)
No 5-LO cleavage can be observed in transfected HeLa or in MM6 cells after stimulation with caspase-activating apoptotic stimuli like TNF alpha, cycloheximide or daunorubicin, or in HeLa cells coexpressing 5-LO, caspase-6 and/or caspase-8. (uni-frankfurt.de)
PM/Scl-75 cleavage is inhibited by several different caspase inhibitors. (biomedcentral.com)
The analysis of PM/Scl-75 cleavage by recombinant caspase proteins shows that PM/Scl-75 is efficiently cleaved by caspase-1, to a smaller extent by caspase-8, and relatively inefficiently by caspase-3 and caspase-7. (biomedcentral.com)
Here we demonstrate that the PM/Scl-75 protein is cleaved in a caspase-dependent manner during apoptosis and that this cleavage occurs in the C-terminal domain of the protein at residue Asp369. (biomedcentral.com)
However, the physiological role of cFLIP cleavage by Caspase-8 remains elusive. (bvsalud.org)
During apoptosis, caspases execute the disassembly of the cellular components by proteolytic cleavage of a variety of substrates, such as poly-(ADP ribose) polymerase (PARP) 3 , DNA-dependent protein kinase (DNA-PK), topoisomerases, and protein kinase C (PKC)δ. (eurogentec.com)
Once the initiator caspases are activated, they process and activate downstream effector caspases, such as caspase-3, -6 and -7, which are responsible for the cleavage of several proteins in dying cells ( Nicholson, 1999 ). (rupress.org)
Apoptosis in response to the ligand CD95L (also known as Fas ligand) is initiated by caspase-8, which is activated by dimerization and self-cleavage at death-inducing signaling complexes (DISCs). (nih.gov)
Previous work indicated that the degree of substrate cleavage by caspase-8 determines whether a cell dies or survives in response to a death stimulus. (nih.gov)
We derived and experimentally validated a minimal model in which cleavage of caspase-8 in the enzymatic domain occurs in an interdimeric manner through interaction between DISCs, whereas prodomain cleavage sites are cleaved in an intradimeric manner within DISCs. (nih.gov)
The activation of caspase-8 by combined intra- and interdimeric cleavage ensures weak signaling at low concentrations of CD95L and strongly accelerated activation at higher ligand concentrations, thereby contributing to precise control of apoptosis. (nih.gov)
The assay is based on detection of cleavage of substrate DEVD-AFC (AFC: 7-amino-4-trifluoromethyl coumarin). (cephamls.com)
upon cleavage of the substrate by CPP32 or related caspases, free AFC emits a yellow-green fluorescence (lmax = 505 nm), which can be quantified using a fluorometer or a fluorescence microtiter plate reader. (cephamls.com)
Proteolytic cleavage or proteolysis is the enzymatic hydrolysis of a peptide bond in a peptide or protein substrate by a family of specialized enzymes termed proteases. (pleasefireme.com)

Activation of caspases-8 and -10 by FLIP(L)". The Biochemical Journal. (wikipedia.org)
8. Prostate apoptosis response 4 (Par-4), a novel substrate of caspase-3 during apoptosis activation. (nih.gov)
16. In lymphatic cells par-4 sensitizes to apoptosis by down-regulating bcl-2 and promoting disruption of mitochondrial membrane potential and caspase activation. (nih.gov)
Most upstream protease of the activation cascade of caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death. (lsbio.com)
BaxDelta2 promotes apoptosis through caspase-8 activation in microsatellite-unstable colon cancer. (lsbio.com)
[ 28 ] Caspase-8 associates with the DISC complex, where it is activated and released, leading to effector caspase activation (notably caspase-3) (Fig. 1). (medscape.com)
[ 29 ] Both intrinsic and extrinsic signaling cascades converge at the point of caspase-3 activation, which is often considered the "point of no return" in apoptosis (rev. in [ 27 , 30 ] ). (medscape.com)
The intrinsic pathway is engaged by a variety of intracellular signals and leads to the activation of Caspase-9. (invivogen.com)
In contrast, the extrinsic pathway is initiated by extracellular perturbations, through death receptors, and induces the activation of Caspase-8. (invivogen.com)
Both the extrinsic and intrinsic apoptotic pathways lead to the activation of Caspase-3 which cleaves more than 500 cellular substrates for death induction. (invivogen.com)
This involves a number of mitochondria-associated factors like BID and cytochrome C, and eventually results in the dimerization of caspase-9 and the subsequent activation of the executioner caspases. (biolegend.com)
Therefore, the activation of caspases and the induction of an incipient immune response seem to be the main triggers for retinal degeneration in this intravitreal HSP27 model. (saussurea.org)
Involved in the activation cascade of caspases responsible for apoptosis execution. (nih.gov)
Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. (nih.gov)
Moreover, the pan-caspase inhibitor Z-VAD-fmk did not prevent cell detachment, but it did prevent apoptosis of the attached cells, indicating that the process of cell detachment, but not apoptosis, is independent of caspase activation in He-MG-treated HCT116 cells ( 20 ). (iiarjournals.org)
Utilizing isogenic HCT116 cell clones, which are either incapable of activating caspase-8 (HCT116/DN.FADD cells), the hallmark event of death receptor-dependent apoptosis, or inhibiting release of cytochrome c and subsequent activation of caspase-9 (HCT116/Bcl-2 cells), the hallmark event of mitochondrion-dependent apoptosis ( 21 - 24 ), we investigated which classical apoptotic mechanism is activated in He-MG-treated cells. (iiarjournals.org)
Our studies indicated that He-MG induced apoptosis not only by activation of caspases -8 and -9, but also by other mechanisms that remain to be identified. (iiarjournals.org)
Taken together, these findings provide the first evidence that TSIIA inhibits growth of NSCLC A549 cells, induces activation of JNK signaling and triggers caspase cascade apoptosis mediated by the release of cytochrome c, which provides a better understanding of the molecular mechanisms of TSIIA on lung cancer. (spandidos-publications.com)
Following exchange of IYG in wt-2B15 for TYS in wt-2B17 at positions 98-100 and transfections into COS-1 cells, 2B17(IYG) generated 10-fold greater in-cellulo caspases 8/3 activations over wt-2B15, while 2B15(TYS) suppressed activation of caspases 8/3 over 50% of wt-2B15 levels. (nih.gov)
Correlating with caspase activation, are changes in membrane symmetry and permeability that can be monitored via Annexin V coupled with a cell-impermeable dye such as 7AAD or PI. (flowmetric.com)
In stress-induced apoptosis, the mitochondrial pathway of caspase activation is believed to be of central importance. (rupress.org)
To determine how caspase-2 is activated, we have studied the formation of a complex that mediates caspase-2 activation. (rupress.org)
Using gel filtration analysis of cell lysates, we show that caspase-2 is spontaneously recruited to a large protein complex independent of cytochrome c and Apaf-1 and that recruitment of caspase-2 to this complex is sufficient to mediate its activation. (rupress.org)
Using substrate-binding assays, we also provide the first evidence that caspase-2 activation may occur without processing of the precursor molecule. (rupress.org)
Our data are consistent with a model where caspase-2 activation occurs by oligomerization, independent of the Apaf-1 apoptosome. (rupress.org)
The apoptotic signals first lead to the activation of so called "initiator caspases," such as caspase-8 and caspase-9. (rupress.org)
These caspases contain specific protein-protein interaction domains in their NH 2 termini that allow them to be recruited to death-signaling complexes promoting their activation by an autocatalytic mechanism (for review see Kumar, 1999 ). (rupress.org)
The FAM FLICA Caspase-8 assay probe allows researchers to assess caspase-8 activation. (immunochemistry.com)
Enhanced Apoptosis and Loss of Cell Viability in Melanoma Cells by Combined Inhibition of ERK and Mcl-1 Is Related to Loss of Mitochondrial Membrane Potential, Caspase Activation and Upregulation of Proapoptotic Bcl-2 Proteins. (immunochemistry.com)
Proliferative and apoptotic homeostasis in various types of cells is regulated by different cytokines and involves Fas-mediated activation of caspase-3 by caspase-8 for programmed cell death. (biomedcentral.com)
Activation of ICE-family proteases/caspases initiates apoptosis in mammalian cells. (cephamls.com)
It ultimately induced the activation of caspase-9, -8, and -3 and apoptotic cell death. (tmu.edu.tw)
Activation of calpains and caspases, and proteolysis of their substrates were detected by immunoblotting. (elsevierpure.com)
Incubation of calpain inhibitor SNJ-1945 or caspase inhibitor z-VAD-fmk was used to confirm activation of specific proteases.ResultsTPEN caused a time-dependent decrease in viable RPE cells. (elsevierpure.com)
Cell death was accompanied by activation of calpain-1, caspase-9, and caspase-3. (elsevierpure.com)
SNJ-1945 inhibited calpain activation and slightly inhibited caspase-9 activation. (elsevierpure.com)
z-VAD-fmk inhibited caspases and calpain-1 activation. (elsevierpure.com)
TPEN did not activate caspase-12.ConclusionsRelative zinc deficiency in RPE cells causes activation of cytosolic calpain and mitochondrial caspase pathways without ER stress. (elsevierpure.com)
Ouabain triggered transient neuronal cell swelling followed by cell shrinkage, accompanied by intracellular Ca 2+ and Na + increase, K + decrease, cytochrome c release, caspase-3 activation, and DNA laddering. (jneurosci.org)
Potassium channel blockers or high K + medium, but not Ca 2+ channel blockade, prevented cytochrome c release, caspase activation, and DNA damage. (jneurosci.org)
All three classes of caspases are activated in HIV infected cells with their activation correlated with the viral infection. (nih.gov)
Blocking of caspase activation dramatically suppressed HIV-1 infection of primary CD4+ T cells and inhibited the viral release. (nih.gov)
Further, HIV accessory gene nef is primarily responsible for inducing caspase activation for viral release. (nih.gov)
These results establish a new paradigm with caspase activation critical for the release phase of HIV life cycle. (nih.gov)

At the heart of this mechanism lies the caspases, a set of highly conserved cysteine proteases that are activated by a variety of proapoptotic stimuli. (medscape.com)
The execution of apoptosis is performed by a family of cysteine proteases known as caspases (for review see Nicholson, 1999 ). (rupress.org)

Expression of apoptosis-related proteins (pro-caspases-3 and -8, Bcl-2, Bax, Bcl-xL and XIAP) was analyzed in immunoblot analysis using monoclonal and polyclonal antibodies. (biomedcentral.com)

We chose to target caspase-3, an executioner caspase, and caspase-8, an initiator caspase, based on the vast amount of information linking their functions to diseases. (nih.gov)
Recent data indicate that in some cells caspase-9 may not be the initiator caspase in stress-mediated apoptosis because caspase-2 is required upstream of mitochondria for the release of cytochrome c and other apoptogenic factors. (rupress.org)

Caspase-10 (EC 3.4.22.63, FLICE2, Mch4, CASP-10, ICE-like apoptotic protease 4, apoptotic protease Mch-4, FAS-associated death domain protein interleukin-1beta-converting enzyme 2) is an enzyme. (wikipedia.org)
Extended subsite profiling of the pyroptosis effector protein gasdermin D reveals a region recognized by inflammatory caspase-11. (academictree.org)
Caspases are activated in a hierarchical order, where initiator caspases (i.e., caspases-8, and -10) function to cleave effector caspases (i.e., caspases-3 and -7), which in turn degrade a number of intracellular protein substrates. (medscape.com)
Inflammasomes are cytosolic multiprotein complexes generally comprised of a sensor and an inflammatory caspase connected to an adaptor protein (ASC). (invivogen.com)
The degradation of 5-LO correlates with increased activity of caspase-8 and -6 and can be prevented by the protein synthesis inhibitor cycloheximide. (uni-frankfurt.de)
FLIP (Flice-like Inhibitory Protein), also known as I-FLICE, CASPER, and FLAME-1, is an apoptosis inhibitory protein with architecture similar to that of Caspases-8 and -10. (rndsystems.com)
This gene encodes a protein which is a member of the cysteine-aspartic acid protease (caspase) family. (nih.gov)
This protein cleaves and activates caspases 3 and 7, and the protein itself is processed by caspase 8. (nih.gov)
In this context, several plant products have exhibited chemopreventative activity against colorectal cancer in vitro and in vivo , including buckwheat protein ( 5 ), resveratrol analogs ( 6 , 7 ), linoleic acid conjugates ( 8 ), curcumin ( 9 ), green tea ( 10 ) and grape seed ( 11 ) extracts, and juice or freeze-dried powder from Brussels sprouts ( 12 ), by targeting various molecular and cellular mechanisms. (iiarjournals.org)
Cellular FLICE-like inhibitory protein (cFLIP) is a crucial regulator of cell death and a substrate of Caspase-8. (bvsalud.org)
In the first pathway, TNF receptor family members recruit Fas-associated protein with death domain (FADD), * an adaptor molecule that in turn recruits caspase-8 to the death-inducing signaling complex (DISC). (rupress.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. (pleasefireme.com)
Besides histones, HDAC6 deacetylates also other substrates including alpha tubulin and HSP90 alpha, and is involved in protein trafficking and degradation, as well as in affecting of cell shape and migration. (abeomics.com)

For example, following death receptor ligation, activated caspase-8 can cleave and activate Bid. (medscape.com)
Once activated, a single executioner caspase can cleave and activate other executioner caspases, ultimately leading to apoptotic destruction of the cell. (eurogentec.com)

We recently showed that treatment of HCT116 cells with a hexane extract of MG (He-MG) can induce arrest at the G 1 -phase of the cell cycle followed by detachment of the cells from the substrate and subsequent apoptosis as assessed by flow cytometry analysis and monitoring of the presence of activated caspases-3, -8, -9 and PARP degradation ( 20 ). (iiarjournals.org)

Kinetic studies of caspase-3 and caspase-8 inhibition were carried out with these urazole ring-containing irreversible peptidomimetics and a known irreversible caspase inhibitor, Z-VAD-fmk. (nih.gov)

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)

FLIP(L) has a C-terminal Caspase-like protease domain which lacks both a catalytic active site and residues that form a substrate-binding pocket. (rndsystems.com)
The CPP32/Caspase-3 Fluorometric Protease Assay Kit provides a simple and convenient means for assaying the DEVD-dependent caspase activity. (cephamls.com)

Growth factor stimulation normally suppresses the intrinsic caspase pathway through PI3K signaling, but loss of this stimulus or the presence of other cellular stresses can activate the intrinsic caspase cascade. (biolegend.com)
The extrinsic mediated apoptosis pathway can be monitored by flow cytometry by measuring caspase 3/7, 8, and poly caspase activity using fluorogenic substrates. (flowmetric.com)
In this pathway, cytochrome c released from mitochondria facilitates the formation of an Apaf-1 apoptosome that recruits and activates caspase-9. (rupress.org)

Engineering Caspase 7 as an Affinity Reagent to Capture Proteolytic Products. (academictree.org)
Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. (nih.gov)

Once cytochrome c accumulates in the cytosol, it complexes with procaspase-9 and Apaf-1 to form the "apoptosome," which in turn activates caspase-3 (Fig. 1). (medscape.com)
DCEG investigators have evaluated the glutathione-S-transferase and cytochrome P-450 families of genes, both of which encode enzymes involved in the metabolism of solvents and other substrates. (cdc.gov)

Mitochondria transmembrane potential and caspase activities measurement. (cdc.gov)
Caspase activity data indicated that TSIIA activated caspase-9 and caspase-3 of mitochondria-mediated apoptosis, but not caspase-8 of receptor-mediated apoptosis, which could be largely rescued by SP600125 (JNK inhibitor). (spandidos-publications.com)
The rates of formation of superoxide and hydrogen peroxide at different electron-donating sites in isolated mitochondria are critically dependent on the substrates that are added, through their effects on the reduction level of each site and the components of the protonmotive force. (biomed.news)
Neurites degenerate at an early stage by an active caspase-independent fragmentation characterized by segregation of energy competent mitochondria. (rupress.org)

In contrast, processing of the typical caspase substrate PARP as well as of cytosolic phospholipase A2 (cPLA2) can be detected in 5-LO positive HeLa cells after stimulation with apoptotic agents. (uni-frankfurt.de)

With the special support of Peptide Institute, PeptaNova established a well sorted stock of biologically active peptides, enzyme - substrates, enzyme - inhibitors and peptide antisera, located in the heart of Europe. (peptanova.de)

Detect caspase-8 activity with the FLICA Caspase-8 Assay Kit. (immunochemistry.com)
Bulk Order Inquiry for FAM-FLICA® Caspase-8 Assay Kit ------- (please add any order requirements, including desired quantity, timing, etc. (immunochemistry.com)

It functions in AUTOPHAGY as a receptor for the degradation of ubiquitinated substrates, and to co-ordinate signaling in response to OXIDATIVE STRESS . (bvsalud.org)
The proteasome is an essential proteinase complex that is involved in the degradation of caspase-3. (biomedcentral.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)

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)
Initiator caspases are said to cleave inactive procaspase dimers that in turn act on executioner caspases (caspases 3, 6 and 7). (eurogentec.com)

It appears that an unknown factor in 5-LO-positive HeLa and MM6 cells protects 5-LO against proteolysis by caspase-6 whereas other caspase substrates remain unaffected. (uni-frankfurt.de)

After being activated by lysyl endopeptidase, it cleaves a thioester substrate. (rndsystems.com)

It induces caspase‑independent cell death when introduced into target cells by perforin (1). (rndsystems.com)

A colorimetric caspase activity assay was performed with pcWNV-Cp-DJY- or pcDNA3.1-transfected cells for caspase-3 (c) or caspase-9 (d) activity. (cdc.gov)
Z-IETD-pNA is a colorimetric caspase-8/granzyme B substrate containing the benzyloxycarbonyl (Z) moiety. (aatbio.com)

From proteomic characterization of caspase substrates, a number of substrate sequences that caspases cleave have been identified with high degrees of specificities, thereby indicating specialized functions for each caspase in cell biology. (eurogentec.com)

As a specificity control, the inhibitor LEHD-FMK for caspase-9 was added to the reactions along with relevant substrate (d). (cdc.gov)
Resurrection of an ancient inflammatory locus reveals switch to caspase-1 specificity on a caspase-4 scaffold. (academictree.org)
Geueke, B. Crytsal structure of BapA complexes with beta-lactam-derived inhibitors illustrate substrate specificity and enantioselectivity of beta-aminopeptidases. (uzh.ch)

Because of their central role in programmed cell death, the caspases are attractive targets for developing new therapeutics against cancer and autoimmunity, myocardial infarction and ischemic damage, and neurodegenerative diseases. (nih.gov)

Using a stopped-flow fluorescence assay, we were able to determine individual kinetic parameters of caspase-3 and caspase-8 inhibition by these inhibitors. (nih.gov)
Z-VAD-fmk and the peptidomimetic inhibitors inhibit caspase-3 and caspase-8 via a three-step kinetic mechanism. (nih.gov)
Inhibition of both caspase-3 and caspase-8 by Z-VAD-fmk and of caspase-3 by the peptidomimetic inhibitors proceeds via two rapid equilibrium steps followed by a relatively fast inactivation step. (nih.gov)

The FLICA reagent FAM-LETD-FMK enters each cell and irreversibly binds to activated caspase-8. (immunochemistry.com)
The remaining green fluorescent signal is a direct measure of the active caspase-8 enzyme activity present in the cell at the time the reagent was added. (immunochemistry.com)

The enzymatic activity of caspase-3 can be detected by the change in PARACEST effect caused by this biotransformation. (arizona.edu)

Isoform 5, isoform 6, isoform 7 and isoform 8 lack the catalytic site and may interfere with the pro-apoptotic activity of the complex. (lsbio.com)
Cell apoptosis was detected by flow cytometry analysis (Annexin V-FITC/PI double-staining assay), the activity and activating cleavages of caspase-3, -8, and -9. (mdpi.com)
ICT's FLICA assay kits are used by researchers seeking to quantitate apoptosis via caspase activity in cultured cells and tissues. (immunochemistry.com)
Activity of caspase-3 was measured using a fluorescent substrate in an enzyme assay. (biomedcentral.com)
To determine how a death ligand stimulus is effectively translated into caspase-8 activity, we assessed this activity over time in single cells with compartmentalized probes that are cleaved by caspase-8 and used multiscale modeling to simultaneously describe single-cell and population data with an ensemble of single-cell models. (nih.gov)
Modeling indicated that sustained membrane-bound caspase-8 activity is followed by transient cytosolic activity, which can be interpreted as a molecular timer mechanism reflected by a limited lifetime of active caspase-8. (nih.gov)
Comparison of the fluorescence of AFC from an apoptotic sample with an uninduced control allows determination of the fold increase in Caspase-3/CPP32 activity. (cephamls.com)

A "smart" PARACEST MRI contrast agent was synthesized to detect caspase-3, which is an important biomarker in apoptosis. (arizona.edu)

Importantly, caspase inhibition suppressed viral release from patient derived CD4+ T cells, from both chronically infected individuals and from aviremic viral reservoirs. (nih.gov)

Caspase mechanisms in the regulation of inflammation. (academictree.org)

A recent paper from this study concerning apoptosis and cell cycle control genes identified caspase 8 as a possible susceptibility gene. (cdc.gov)

The data showed that TSIIA significantly suppressed the proliferation of A549 cells in a dose-dependent manner, with IC50 values of 16.0±3.7 and 14.5±3.3 µM at 48 h as determined by Cell Counting Kit-8 (CCK-8) assay and clone formation assay, respectively. (spandidos-publications.com)
Caspases are present as zymogens in most animal cells and are activated in response to apoptotic signals. (rupress.org)
This in vitro assay employs the fluorescent inhibitor probe FAM-LETD-FMK to label active caspase-8 enzyme in living cells. (immunochemistry.com)
Though the increased MDR1 expression wasn't functionally relevant as sensitivity to doxorubicin, a Pglycoprotein substrate, was not altered in cells in comparison to CEM cells using cytotoxicity assays. (hormonespathway.com)
Uptake of Daunorubicin, still another P glycoprotein substrate, wasn't paid off in these same cells as determined by flow cytometry. (hormonespathway.com)

Mol Cancer Ther (2002) 1 (8): 639-649. (aacrjournals.org)

Caspases play important roles in apoptosis and inflammation. (immunochemistry.com)

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Cleavage18

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Proteases2

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Initiator caspase2

Protein13

Cleave and activate2

Assessed by flow cytometry1

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Proteins1

Protease2

Pathway3

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20021

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