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(aspartyl)2-rhodamine 110 + H2O
?
Ac-IEPD-7-amido-4-methylcoumarin + H2O
Ac-IEPD + 7-amino-4-methylcoumarin
37°C
-
-
?
Ac-IEPD-AMC + H2O
Ac-IEPD + AMC
37°C
-
-
?
Ac-IETD-4-methylcoumarin 7-amide + H2O
Ac-IETD + 7-amino-4-methylcoumarin
-
an artificial caspase-8 substrate
-
-
?
Ac-IETD-7-amido-4-methylcoumarin + H2O
Ac-IETD + 7-amino-4-methylcoumarin
Ac-Leu-Glu-Thr-Asp-7-amido-4-trifluoromethylcoumarin + H2O
Ac-Leu-Glu-Thr-Asp + 7-amino-4-trifluoromethylcoumarin
-
-
-
?
acetyl-DEVD-4-nitroanilide + H2O
acetyl-DEVD + 4-nitroaniline
-
-
-
?
acetyl-DEVD-7-amido-4-methylcoumarin + H2O
acetyl-DEVD + 7-amino-4-methylcoumarin
-
-
-
-
?
acetyl-DEVD-p-nitroanilide + H2O
acetyl-DEVD + p-nitroaniline
-
49% of the activity with acetyl-IETD-p-nitroanilide
-
-
?
acetyl-IETD-4-nitroanilide + H2O
acetyl-IETD + 4-nitroaniline
acetyl-IETD-7-amido-4-fluoromethylcoumarin + H2O
acetyl-IETD + 7-amino-4-fluoromethylcoumarin
acetyl-IETD-p-nitroanilide + H2O
acetyl-IETD + p-nitroaniline
-
-
-
-
?
acetyl-Ile-Glu(OMe)-Thr-Asp(OMe)-7-amido-4-trifluoromethylcoumarin + H2O
acetyl-Ile-Glu(OMe)-Thr-Asp(OMe) + 7-amino-4-trifluoromethylcoumarin
acetyl-Ile-Glu-Thr-Asp-7-amino-4-fluoromethylcoumarin + H2O
Ac-IETD + 7-amino-4-fluoromethylcoumarin
37°C, pH 7.4
-
-
?
acetyl-LEHD-p-nitroanilide + H2O
acetyl-LEHD + p-nitroaniline
-
142% of the activity with acetyl-IETD-p-nitroanilide
-
-
?
acetyl-VDVAD-p-nitroanilide + H2O
acetyl-VDVAD + p-nitroaniline
-
36% of the activity with acetyl-IETD-p-nitroanilide
-
-
?
acetyl-VEID-p-nitroanilide + H2O
acetyl-VEID + p-nitroaniline
-
76% of the activity with acetyl-IETD-p-nitroanilide
-
-
?
acetyl-WEHD-p-nitroanilide + H2O
acetyl-WEHD + p-nitroaniline
-
64% of the activity with acetyl-IETD-p-nitroanilide
-
-
?
alpha-fodrin + H2O
?
-
-
-
-
?
Atg3 protein + H2O
?
-
-
-
?
BAP31 + H2O
?
cleavage results in a proapoptotic p20 fragment
-
-
?
basic transcription factor 3 + H2O
?
-
-
-
-
?
Bcl-2 protein Bid + H2O
?
cleavage results in a proapoptotic p15 tBid fragment
-
-
?
benzyloxycarbonyl-IETD-7-amido-4-trifluoromethylcoumarin + H2O
benzyloxycarbonyl-IETD + 7-amino-4-trifluoromethylcoumarin
-
-
-
-
?
beta-catenin + H2O
?
-
-
-
-
?
BH3-only protein Bid + H2O
?
-
-
-
?
Bid peptide + H2O
truncated Bid peptide + ?
Bid protein + H2O
?
-
-
-
-
?
Bid protein + H2O
cleaved Bid protein
-
i.e. BH3 interacting domain death agonist protein
-
-
?
Ca2+/calmodulin-dependent protein kinase-like kinase + H2O
?
cleavage generates a 43 kDa C-terminal fragment and a small N-terminal fragment with proapoptotic activity
-
-
?
carbonic anhydrase XIV + H2O
?
-
cleaved at Asp53
-
-
?
carboxypeptidase E + H2O
?
-
-
-
-
?
caspase-3 + H2O
?
-
-
-
-
?
cellular FLIP long form + H2O
?
-
-
-
?
cellular inhibitor of apoptosis 1 + H2O
?
DEVD-rhodamine + H2O
rhodamine + DEVD
-
-
-
?
Dopey family membrane 1 + H2O
?
-
-
-
-
?
evolutionarily related interleukin-1beta converting enzyme + H2O
?
-
ERICE i.e. evolutionarily related interleukin-1beta converting enzyme, cleavage at LEED289-/-, processing leads to the generation of two subunits
-
-
?
FLIPL + H2O
?
-
the cleavage sequence for caspase-8 is LEVD/G
-
-
?
fluorescein isothiocyanate + H2O
?
37°C, pH 7.4
-
-
?
glutaredoxin-1 + H2O
?
-
murine or human protein substrate, the putative cleavage site of caspase-8, amino acids 43-46 EFVD and 56-59 AIQD, which has predicted affiffinity toward glutamic and aspartic acid residues
cleavage produces a 8 kDA fragment
-
?
Golgi associated PDZ and coiled-coil motif containing trancription variant 1 + H2O
?
-
-
-
-
?
HDAC-7 + H2O
?
-
the cleavage sequence for caspase-8 is LETD/G
-
-
?
IEPD-7-amido-4-methylcoumarin + H2O
IEPD + 7-amino-4-methylcoumarin
-
-
-
-
?
IETD-4-nitroanilide + H2O
IETD + 4-nitroaniline
IETD-7-amido-4-trifluoromethylcoumarin + H2O
IETD + 7-amino-4-trifluoromethylcoumarin
Ile-Glu-Thr-Asp-4-nitroanilide + H2O
Ile-Glu-Thr-Asp + 4-nitroaniline
-
-
-
-
?
kinase anchor protein 1 + H2O
?
-
-
-
-
?
LETD-4-nitroanilide + H2O
LETD + 4-nitroaniline
-
-
-
-
?
N-acetyl-IETD-4-nitroanilide + H2O
N-acetyl-IETD + 4-nitroaniline
N-acetyl-IETD-4-nitroanilide + H2O
N-acetyl-IETD + 4-nitroaniline + H2O
N-acetyl-IETD-4-trifluoromethylcoumarin 7-amide + H2O
N-acetyl-IETD + 7-amino-4-trifluoromethylcoumarin
nuclear export signal-LQTDG + H2O
?
-
-
-
-
?
p21-activated kinase 2 + H2O
?
separates the N-terminal regulatory domain from the C-terminal catalytic domain
-
-
?
pro-caspase-3 + H2O
caspase-3 + ?
procaspase-10 + H2O
caspase-3 + ?
-
the cleavage sequence in procaspase-10, catalytically inactive C285A mutant, for caspase-8 is IEAD/A
-
-
?
procaspase-3 + H2O
active caspase-3 + ?
procaspase-3 + H2O
caspase-3 + ?
procaspase-6 + H2O
caspase-6 + ?
procaspase-7 + H2O
caspase-3 + ?
-
the cleavage sequence in procaspase-7, catalytically inactive C285A mutant, for caspase-8 is IQAD/S
-
-
?
procaspase-8 + H2O
caspase-8 + ?
receptor-indicating protein + H2O
?
vezatin + H2O
?
-
cleaved at Asp655
-
-
?
additional information
?
-
(aspartyl)2-rhodamine 110 + H2O
?
-
-
-
-
?
(aspartyl)2-rhodamine 110 + H2O
?
-
-
-
-
?
(aspartyl)2-rhodamine 110 + H2O
?
-
-
-
-
?
(aspartyl)2-rhodamine 110 + H2O
?
-
-
-
-
?
(aspartyl)2-rhodamine 110 + H2O
?
-
-
-
-
?
(aspartyl)2-rhodamine 110 + H2O
?
-
-
-
-
?
Ac-IETD-7-amido-4-methylcoumarin + H2O
Ac-IETD + 7-amino-4-methylcoumarin
-
-
-
-
?
Ac-IETD-7-amido-4-methylcoumarin + H2O
Ac-IETD + 7-amino-4-methylcoumarin
-
-
-
-
?
acetyl-IETD-4-nitroanilide + H2O
acetyl-IETD + 4-nitroaniline
-
-
-
-
?
acetyl-IETD-4-nitroanilide + H2O
acetyl-IETD + 4-nitroaniline
-
-
-
?
acetyl-IETD-7-amido-4-fluoromethylcoumarin + H2O
acetyl-IETD + 7-amino-4-fluoromethylcoumarin
-
-
-
-
?
acetyl-IETD-7-amido-4-fluoromethylcoumarin + H2O
acetyl-IETD + 7-amino-4-fluoromethylcoumarin
-
-
-
?
acetyl-Ile-Glu(OMe)-Thr-Asp(OMe)-7-amido-4-trifluoromethylcoumarin + H2O
acetyl-Ile-Glu(OMe)-Thr-Asp(OMe) + 7-amino-4-trifluoromethylcoumarin
-
-
-
-
?
acetyl-Ile-Glu(OMe)-Thr-Asp(OMe)-7-amido-4-trifluoromethylcoumarin + H2O
acetyl-Ile-Glu(OMe)-Thr-Asp(OMe) + 7-amino-4-trifluoromethylcoumarin
-
-
-
-
?
BID + H2O
?
-
-
-
-
?
BID + H2O
?
-
a 15000 Da C-terminal frament and a 14000 Da N-terminal fragment are generated by caspase-8 cleavage at T58-/-D59
-
-
?
BID + H2O
?
-
a 15000 Da C-terminal frament and a 14000 Da N-terminal fragment are generated by caspase-8 cleavage at T58-/-D59. While full-length BID is localized in cytosol, truncated BID translocates to mitochondria and thus transduces apoptotic signals from cytoplasmic membrane to mitochondria. BID is a mediator of mitochondrial damage induced by Casp8
-
-
?
BID + H2O
?
-
the cleavage sequences for caspase-8 are IEAD/S and LQTD/G
-
-
?
Bid + H2O
tBid + ?
-
Bid is a caspase-8 substrate and that its cleavage can be crucial for CD95-induced apoptosis. Caspase-8-mediated cleavage of Bid into a pro-apoptotically active, truncated form provides the link between death receptor stimulation and mitochondrial apoptotic events
-
-
?
Bid + H2O
tBid + ?
-
i.e. BH3 interacting domain death agonist
-
-
?
Bid + H2O
tBid + ?
-
caspase-8 cleaves Bid at Asp60 leading to the release of a truncated form containing the C-terminal part of the protein, 15 kDa. Cleavage of Bid by caspase-8 removes the N-terminal portion of the protein which, when still linked to the C-terminal p15 portion inhibits the pro-apoptotic function of the latter
-
-
?
Bid peptide + H2O
?
-
-
-
-
?
Bid peptide + H2O
?
-
a specific caspase-8 substrate
-
-
?
Bid peptide + H2O
?
-
CTX III, from crude venom of Naja naja atra, inhibits proliferation of human leukemia K562 cells by G2/M phase arresting and apoptosis which is associated with the activation of caspase-8 and cytochrome c release as well as the p38 and c-Jun N-terminal protein kinase phosphorylation signaling pathway in vitro and in vivo, caspase-8-dependent Bid-Bax pathway, overview
-
-
?
Bid peptide + H2O
?
-
upon cleavage by caspase-8, Bid peptide activates Bax peptide
-
-
?
Bid peptide + H2O
truncated Bid peptide + ?
-
-
-
-
?
Bid peptide + H2O
truncated Bid peptide + ?
-
-
-
-
?
cellular inhibitor of apoptosis 1 + H2O
?
i.e. cIAP-1, TRAIL-induced degradation of cIAP-1 requires caspase 8 activity, and it is, at least in part, due to direct cleavage of cIAP-1 by caspase 8
-
-
?
cellular inhibitor of apoptosis 1 + H2O
?
i.e. cIAP-1, degradation. No activity with cIAP-2. In vitro substrate is recombinant human cIAP-1
-
-
?
CYLD + H2O
CYLDp25 + ?
-
key substrate processed by caspase 8 to block necrosis, CYLD is a key requirement for necrosis
-
-
?
CYLD + H2O
CYLDp25 + ?
-
caspase 8 directly cleaves CYLD after Asp 215, an Asp215 CYLD substitution mutant cannot be cleaved by caspase 8
-
-
?
CYLD + H2O
CYLDp25 + ?
-
key substrate processed by caspase 8 to block necrosis, CYLD is a key requirement for necrosis of L929 fibrosarcoma cells
-
-
?
CYLD + H2O
CYLDp25 + ?
-
caspase 8 directly cleaves CYLD after Asp 215, an Asp215 CYLD substitution mutant cannot be cleaved by caspase 8
-
-
?
FLIPL protein + H2O
?
-
-
-
-
?
FLIPL protein + H2O
?
-
processing of free FLIPL by caspase-8, FLIPL cleavage increases the recruitment of caspase-8
-
-
?
FLIPL protein + H2O
?
-
processing of free FLIPL by caspase-8
-
-
?
FLIPL protein + H2O
?
-
processing of free FLIPL by caspase-8, FLIPL cleavage increases the recruitment of caspase-8
-
-
?
FLIPL protein + H2O
?
-
processing of free FLIPL by caspase-8
-
-
?
HER-2 + H2O
?
-
-
-
-
?
HER-2 + H2O
?
37°C, HER-2 double mutant MT34, carrying the mutation D1125A/D837A
-
-
?
HER-2 + H2O
?
37°C, HER-2 double mutant MT35, carrying the mutation D1125A/D1087A, completely resistant to proteolysis
-
-
?
HER-2 + H2O
?
37°C, HER-2 double mutant MT36, carrying the mutation D1125A/D1115A
-
-
?
HER-2 + H2O
?
37°C, HER-2 mutant MT1, carrying the mutation D1012A
-
-
?
HER-2 + H2O
?
37°C, HER-2 mutant MT2, carrying the mutation D1019A
-
-
?
HER-2 + H2O
?
37°C, HER-2 mutant MT3, carrying the mutation D1125A, partially resistant to proteolysis
-
-
?
HER-2 + H2O
?
37°C, wild-type HER-2
-
-
?
IETD-4-nitroanilide + H2O
IETD + 4-nitroaniline
-
-
-
-
?
IETD-4-nitroanilide + H2O
IETD + 4-nitroaniline
-
-
-
?
IETD-4-nitroanilide + H2O
IETD + 4-nitroaniline
-
-
-
?
IETD-4-nitroanilide + H2O
IETD + 4-nitroaniline
-
-
-
?
IETD-7-amido-4-trifluoromethylcoumarin + H2O
IETD + 7-amino-4-trifluoromethylcoumarin
-
-
-
?
IETD-7-amido-4-trifluoromethylcoumarin + H2O
IETD + 7-amino-4-trifluoromethylcoumarin
-
-
-
-
?
IETD-7-amido-4-trifluoromethylcoumarin + H2O
IETD + 7-amino-4-trifluoromethylcoumarin
-
a specific caspase-8 substrate
-
-
?
interleukin-21 + H2O
?
-
-
the CASP8-cleaved form of IL21R does not induce phosphorylation at Tyr705 of STAT3
-
?
interleukin-21 + H2O
?
-
cleaved at Asp344
-
-
?
N-acetyl-IETD-4-nitroanilide + H2O
N-acetyl-IETD + 4-nitroaniline
-
-
-
?
N-acetyl-IETD-4-nitroanilide + H2O
N-acetyl-IETD + 4-nitroaniline
-
-
-
?
N-acetyl-IETD-4-nitroanilide + H2O
N-acetyl-IETD + 4-nitroaniline + H2O
-
-
-
?
N-acetyl-IETD-4-nitroanilide + H2O
N-acetyl-IETD + 4-nitroaniline + H2O
-
-
-
?
N-acetyl-IETD-4-trifluoromethylcoumarin 7-amide + H2O
N-acetyl-IETD + 7-amino-4-trifluoromethylcoumarin
-
-
-
-
?
N-acetyl-IETD-4-trifluoromethylcoumarin 7-amide + H2O
N-acetyl-IETD + 7-amino-4-trifluoromethylcoumarin
-
-
-
-
?
parkin + H2O
?
-
cleavage at Asp126-Ser127
-
-
?
parkin + H2O
?
-
cleavage at Asp126-Ser127. Caspase-1 and caspase-8 dependent parkin cleavage in sporadic Parkinsons disease may play an important role in the degenerative process by initiating a vicious circle that leads to the accumulation of toxic parkin substrates, e.g. alpha-synuclein
-
-
?
pro-caspase-3 + H2O
caspase-3 + ?
-
-
-
-
?
pro-caspase-3 + H2O
caspase-3 + ?
-
caspase-3 is activated through caspase-8 during H2O2-induced apoptosis in HeLa cells
-
-
?
procaspase-3 + H2O
?
-
-
-
-
?
procaspase-3 + H2O
?
results in a p11 and p20 fragment
-
-
?
procaspase-3 + H2O
?
-
caspase-8 induces apoptosis by directly activating caspase-3, which in turn causes the characteristic features of apoptosis, including DNA fragmentation and cell death
-
-
?
procaspase-3 + H2O
active caspase-3 + ?
-
direct activation by caspase-8 in type I cells
-
-
?
procaspase-3 + H2O
active caspase-3 + ?
-
activation by caspase-8
-
-
?
procaspase-3 + H2O
caspase-3 + ?
-
-
-
-
?
procaspase-3 + H2O
caspase-3 + ?
-
pro-caspase-3 is a major physiologic target of caspase-8
-
-
?
procaspase-3 + H2O
caspase-3 + ?
-
activation
-
-
?
procaspase-3 + H2O
caspase-3 + ?
-
activation of effector caspase-3 by the initiator caspase-8
-
-
?
procaspase-3 + H2O
caspase-3 + ?
-
cleavage of caspases 3 and 6 by caspase-8 results in apoptosis
-
-
?
procaspase-3 + H2O
caspase-3 + ?
-
in some cells, active caspase-8 is sufficient to activate caspase-3 directly. In other cells, however, caspase-8 indirectly mediates caspase-3 activation by cleaving the proapoptotic Bcl-2 family member Bid, which induces mitochondrial cytochrome c release
-
-
?
procaspase-3 + H2O
caspase-3 + ?
-
procaspase-8 activation in the death-inducing signalling complex, DISC, leads to cleavage of procaspase-3 and engagement of the cellular machinery associated with the type I extrinsic apoptotic pathway
-
-
?
procaspase-3 + H2O
caspase-3 + ?
-
-
-
-
?
procaspase-3 + H2O
caspase-3 + ?
-
activation
-
-
?
procaspase-3 + H2O
caspase-3 + ?
-
in some cells, active caspase-8 is sufficient to activate caspase-3 directly. In other cells, however, caspase-8 indirectly mediates caspase-3 activation by cleaving the proapoptotic Bcl-2 family member Bid, which induces mitochondrial cytochrome c release
-
-
?
procaspase-3 + H2O
caspase-3 + ?
-
the cleavage sequence in procaspase-3, catalytically inactive C285A mutant, for caspase-8 is IETD/S
-
-
?
procaspase-6 + H2O
caspase-6 + ?
-
activation
-
-
?
procaspase-6 + H2O
caspase-6 + ?
-
cleavage of caspases 3 and 6 by caspase-8 results in apoptosis
-
-
?
procaspase-8 + H2O
caspase-8 + ?
-
caspase-8 is initially synthesized as a single-chain zymogen, procaspase-8, and activated by autocleavage at proteolytic sites Asp126, Asp216, Asp374, and Asp384 after recruitment to DISCs by N-terminal two tandem DEDs of procaspase-8. The proximity-driven dimerization of procaspase-8 is attributable to initiate autocleavage of procaspase-8 involving intra-dimeric and inter-dimeric attack. Dimerized procaspase-8 which achieves enzymatical competency specifically processes one another, while mature caspase-8 can cleave effector caspases and some other substrates. Dramatical conformation changes of the linker region undergo in order to bring cleavage sites, Asp374 and Asp384, to the vicinity of catalytic residue Cys283 from other protomer during dimerization of procaspase-8. Separation of the large and small subunit after intra-dimeric cleavage in the linker region between the large and small subunit renders the linker region between the large subunit and the prodomain of caspase-8 susceptible for the further inter-dimeric cleavage
the C- and N-terminal end, of linker region are released with cleavage at Asp374 and Asp384 before separation of the large and small subunit
-
?
procaspase-8 + H2O
caspase-8 + ?
-
the autocleavage sequences of procaspase-8 monomers are VETD/S and LEMD/L, and of procaspase-8 dimers VETD/S and LEMD/L
-
-
?
receptor-indicating protein + H2O
?
separates the N-terminal kinase from the C-terminal death domain
-
-
?
receptor-indicating protein + H2O
?
separates the N-terminal kinase from the C-terminal death domain
-
-
?
RIPK1 + H2O
?
-
-
-
-
?
RIPK1 + H2O
?
-
Lys63-linked RIPK1 ubiquitylation is required to render RIPK1 susceptible to caspase 8-mediated cleavage, the mechanism by which RIPK1 signalling is suppressed in this context
-
-
?
RIPK1 + H2O
?
-
the cleavage sequence for caspase-8 is LQLD/C
-
-
?
additional information
?
-
-
endothelial cell apoptosis induced by bacteria-activated platelets requires caspase-8 and -9 and generation of reactive oxygen species
-
-
?
additional information
?
-
-
caspase-8 is possibly involved in the apoptotic cell death in batch and fed-batch cultures of CHO cells
-
-
?
additional information
?
-
-
role of caspase-8 in the apoptotic signal pathway
-
-
?
additional information
?
-
Mch2 and ICH1 are effectively cleaved only in the presence of native extract
-
-
?
additional information
?
-
-
the preferred cleavage sequence is LETD-/-
-
-
?
additional information
?
-
-
the preferred cleavage sequence is LETD-/-
-
-
?
additional information
?
-
the catalytic triad in caspase-8 comprises C260, H317 and the backbone carbonyl oxygen atom of R258, which points towards the Nepsilon atom of H317
-
-
?
additional information
?
-
-
the catalytic triad in caspase-8 comprises C260, H317 and the backbone carbonyl oxygen atom of R258, which points towards the Nepsilon atom of H317
-
-
?
additional information
?
-
caspase-8L acts as an inhibitor of caspase-8 by interfering with the binding of caspase-8 to FADD, i.e. Fas-associated protein with death domain, and is involved in the regulation of Fas-mediated apoptosis
-
-
?
additional information
?
-
-
caspase-8L acts as an inhibitor of caspase-8 by interfering with the binding of caspase-8 to FADD, i.e. Fas-associated protein with death domain, and is involved in the regulation of Fas-mediated apoptosis
-
-
?
additional information
?
-
caspase-8 is an initiator enzyme in the Fas-mediated pathway of which the downstream executioner caspase-3 is a physiological target
-
-
?
additional information
?
-
initiator enzyme in apoptosis
-
-
?
additional information
?
-
-
initiator enzyme in apoptosis
-
-
?
additional information
?
-
-
the enzyme acts as apoptosis initiator. Animals deficient in caspase-8 are embryonically lethal at approximately E12.5. Abnormal heart development and vascular hyperemia, EF resistant to Fas, TNF-alpha, and DR3 but exhibit normal sensitivity to UV, etoposide, low serum and staurosporine, death receptor signaling to JNK and NF-kappaB intact
-
-
?
additional information
?
-
-
FLICE binds to the death effector domain of FADD and upon overexpression induces apoptosis that is blocked by the ICE family inhibitors, CrmA and v-VAD-fmk
-
-
?
additional information
?
-
-
FLICE is the first in a cascade of ICE-like proteases activated by CD95. Active FLICE is released into the cytosol, where it can activate a cascade of ICE-like proteases
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-
?
additional information
?
-
-
the enzyme is responsible for activating a protease cascade after Fas-receptor ligation, leading to cell death. Mch5 is the most upstream protease that receives the activation signal from the Fas-receptor to initiate the apoptotic protease cascade that leads to activation of ICE-like proteases (TX, ICE, and ICE-relIII), Ced-3-like proteases (CPP32, Mch2, Mch3, Mch4 and Mch6) and the ICH-1 protease
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-
?
additional information
?
-
preferential recruitment of procaspase-8L by the BAP31 complex at the endoplasmic reticulum suggests an additional pathway for regulating initiator caspase-8 during apoptosis
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-
?
additional information
?
-
-
caspase-8 has a postnatal role in immune activation of native lymphocytes
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-
?
additional information
?
-
-
caspase-8 occupies an essential and apical position in the fas signaling pathway and suggests that caspase-8 may participate broadly in multiple apoptotic pathways
-
-
?
additional information
?
-
MACH is the most upstream enzymatic component in the Fas/APO-1- and p55-R-induced cell death signaling cascade
-
-
?
additional information
?
-
CD95 and TNFR-1 death receptors initiate apoptosis by recruiting FLICE/MACH, which represents the apical triggering member of the protease death cascade and a target for the cell death inhibitor CrmA
-
-
?
additional information
?
-
the initiator caspase-8 activates other downstream caspases that are incapable of autocatalytic processing and activation
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-
?
additional information
?
-
-
the initiator caspase-8 activates other downstream caspases that are incapable of autocatalytic processing and activation
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-
?
additional information
?
-
-
caspase-8 inhibits androgen receptor transcriptional activity by disrupting androgen receptor amino-terminal and carboxy-terminal interaction and inhibiting androgen induced androgen receptor nuclear localization
-
-
?
additional information
?
-
-
activation of caspase-8 by glycogen synthase kinase-3 inhibitors can overcome the striking resistance to tumor necrosis factor-related apoptosis-inducing ligand, TRAIL, diplayed by hepatocellular carcinoma cells in contrast to normal heptocytes, overview
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-
?
additional information
?
-
-
caspase 8 activation induced by C5a leads to cell death if protein synthesis of antiapoptotic proteins are blocked
-
-
?
additional information
?
-
-
caspase 8 is an initiator caspase that plays an important role in the Fas-Fas ligand pathway
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-
?
additional information
?
-
-
caspase family proteases are key proteins in apoptotic signaling pathways, which are activated in both the death receptor-mediated and the mitochondria-mediated apoptosis pathways
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-
?
additional information
?
-
-
caspase-3 is an initiator caspase. Increased caspase-8 activation is involved in initiation of apoptosis, inhibition of caspase-8 impairs Leptospira interrogans-induced caspase-3 and -6 activation, as well as PARP and lamin A/C cleavage and apoptosis, overview. Leptospira interrogans-induced apoptosis in macrophages is mediated by caspase-3 and -6 activation through a FADD-caspase-8-dependent pathway, independently of mitochondrial cytochrome c-caspase-9-dependent signaling, regulation, overview
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-
?
additional information
?
-
-
caspase-8 expression is reduced in B-cell chronic lymphocytic leukemia
-
-
?
additional information
?
-
-
caspase-8 is activated by the death receptor pathway leading to apoptosis. Human herpesvirus HHV-6A-induced apoptosis is associated with activation of caspase-8, caspase-9, and caspase-3, suggesting the involvement of death receptor and mitochondrial signaling pathways, overview. HHV-6 differentially influences the functions of naive T cells and different subsets of memory CD4+ and CD8+ T cells, which in part may be due to differential susceptibility to HHV-6A-induced apoptosis, overview
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-
?
additional information
?
-
-
caspase-8 is activated downstream of the death receptor signaling or via death receptor-independent pathway
-
-
?
additional information
?
-
-
caspase-8 is an initiator caspase. Procaspase-8 activation is essentially involved in apoptosis induced by selected nutritional free fatty acids, mechanisms, overview
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-
?
additional information
?
-
-
caspase-8 is involved in apoptosis in multiple myeloma and is the main initiator caspase in the tumor necrosis factor-related apoptosis-inducing pathway overview. c-FLIPL, is the main endogenous regulator of caspase-8 activation, increases with bortezomib treatment but the combination of Apo2L/TRAIL and bortezomib led to a decrease of both FLIP isoforms, regulation, overview
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-
?
additional information
?
-
-
caspase-8, an initiator caspase, is not involved in MDA-MB-231 apoptotic cell death, overview. Caspase-8 is activated when procaspase-8 is cleaved subsequently from the recruitment of Fas associated protein with death domain, FADD, to the death-effector domain site of procaspase-8 during the oligomerization of death receptor and its ligand
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-
?
additional information
?
-
-
caspases 3, 8 and 9 are essential to rhein-induced apoptosis, inhibitors of caspases 3, 8 and 9 are efficiently blocked by rhein-induced apoptosis in TNF-alpha-treated human aortic smooth muscle cells, overview
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-
?
additional information
?
-
-
caspases are a family of aspartate-specific cysteine proteases responsible for the biochemical and morphological changes that occur during the execution phase of apoptosis, model of the intrinsic pathway: caspase-9, the apical caspase, directly processes and activates the effector caspases, caspase-3 and -7, and then active caspase-3, but not caspase-7, processes caspase-2 and -6, and subsequently the activated caspase-6 processes caspase-8 and -10. Caspase-9 but not -8 is required for etoposide-induced processing of caspase-2 and -6. Caspase processing pathways and regulation, overview
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-
?
additional information
?
-
-
extrinsic and intrinsic apoptosis induced by equol in human breast cancer MDA-MB cells does not involve caspase-8 activation of receptor-mediated apoptosis, overview
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-
?
additional information
?
-
-
Fas ligand, a type II transmembrane protein expressed on the surface of cells, induces apoptotic cell death by binding to its receptor Fas, resulting in recruitment of the Fas-associated death domain protein and caspase 8 zymogens to the receptor and the formation of the death-inducing signalling complex, after which the caspases cascade can be activated. Defects in the Fas/FasL apoptotic signalling pathway provide a survival advantage to cancer cells and may be implicated in tumorigenesis
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-
?
additional information
?
-
-
Fas-associated death domain-like IL-1beta-converting enzyme inhibitory protein, c-FLIP, can suppress Fas-mediated apoptosis by inhibition of caspase-8 activation. Caspase-8 is active via the death receptor-dependent pathway, or extrinsic pathway, complex formation and mechanism, overview
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-
?
additional information
?
-
-
harmol activates caspase-8 to 334% and induces apoptosis by caspase-8 activation independently on Fas/Fas ligand interaction in human lung carcinoma H-596 cells, but not in H-596, H-226, and A-549 cells
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-
?
additional information
?
-
-
homocysteine-mediated EPC toxicity is due to apoptosis involving caspase-8, cytochrome c release, and caspase-3 activation, overview
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-
?
additional information
?
-
-
initial activation of caspase-8 causes degradation of glutaredoxin-1, resulting in S-glutathionylation of Fas at cysteine 294, which subsequently enhances binding of FasL, aggregation of Fas, accumulation of Fas in lipid rafts, DISC assembly, and further activation of caspases, causing a propagation of apoptotic cell death. activation of caspases is required for degradation of glutaredoxin-1 and S-glutathionylation of Fas, engagement of Fas causes a rapid activation of caspase-8. Overexpression of Grx1 prevents increases in S-glutathionylation of Fas and attenuates caspase activation and apoptosis in response to receptor ligation. Cleaved caspase-8 and -3 demonstrate an association between active caspases and Grx1 in cells after ligation of Fas, whereas in control cells, these associations are not observed, regulation, overview
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-
?
additional information
?
-
-
interferon regulatory factor 5, IRF-5, promotes apoptosis upon signaling through tumor necrosis factor-related apoptosis-inducing ligand, TRAIL, death receptors, DR. IRF-5 is involved in DR signaling upstream of caspase-8 and induces caspase-8 activation, mechanisms, overview
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-
?
additional information
?
-
-
involvement of lipid raft aggregates containing recruited Fas/CD95 death receptor, Fas-associated death domain-containing protein, FADD, and procaspase-8 in the induction of apoptosis in human T-cell leukemia Jurkat cells by the antitumor drug edelfosine. Specific inhibition of caspase-8 prevents the apoptotic response triggered by edelfosine
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?
additional information
?
-
-
LRRK2-induced neuronal death is caspase-8-dependent. Fas death domain, FADD, recruits caspase-8 to LRRK2. FADD transduces death signals by binding to ligand-activated Fas via its DD and recruiting and activating caspase-8 via its death-effector domain, DED. The Parkinson disease protein leucine-rich repeat kinase 2 transduces death signals via Fas-associated protein with death domain and caspase-8 in a cellular model of neurodegeneration. In primary neuronal culture LRRK2-mediated neurodegeneration is prevented by the functional inhibition of FADD or depletion of caspase-8, two key elements of the extrinsic cell death pathway, overview
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?
additional information
?
-
-
methotrexate-induced apoptosis does not involve activation of caspase-8, but of caspase-9, overview. Caspase-8 is recruited to an apoptosis-inducing signaling complex when apoptotic receptors are oligomerized after binding of specific ligands. Active caspase-8 can either act directly on downstream executioner caspases, or indirectly on mitochondria
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?
additional information
?
-
-
netrin-1 siRNA-induced H-358 cell death is mediated by caspase-3 and -9 activities, but not by caspase-8 activity
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?
additional information
?
-
-
stem-cell-like glioma cells are resistant to tumour necrosis factor -related apoptosis-inducing ligand, TRAIL/Apo2L and exhibit down-regulation of caspase-8 by promoter methylation
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?
additional information
?
-
-
The cysteine protease caspase-8 plays an essential role in apoptosis induced by death receptors, caspase-8 mediates mitochondrial release of pro-apoptotic proteins in a manner independent of its proteolytic activity in apoptosis induced by the protein synthesis inhibitor acetoxycycloheximide in human leukemia Jurkat cells. Bid is cleaved not by caspase-8 but by other caspases in Ac-CHX-treated cells and is not involved in mitochondrial release of proapoptotic proteins
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?
additional information
?
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-
caspases contain a reactive cysteine critical for enzymatic activity. Increased S-glutathionylation of Fas, caspase-8 activity, and cell death in cells lacking Grx1
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?
additional information
?
-
-
Arg-Gly-Asp-Ser directly and specifically binds pro-caspase-8
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?
additional information
?
-
-
caspase-4 activation requires the action of upstream initiator components such as caspase-8
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?
additional information
?
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-
FADD-like interleukin-1beta-converting enzyme-inhibitory protein is an antagonist of caspases-8
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?
additional information
?
-
-
caspase-8 is involved in activation of acid sphingomyelinase induced by TNF, but caspase-8 does not display firm association neither with caspase-7 nor with A-SMase, overview. Direct binding of caspase-8 to TNF-R1 on internalized receptosomes
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?
additional information
?
-
-
caspase-8 performs self-cleavage to give the processed active dimer. Within the caspase-8/FLIPL heterodimer, caspase-8 prefers to process FLIPL over itself
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?
additional information
?
-
-
generation of an NCtagged sTMP library and screening for CASP8 substrates, CASP8-cleavable sTMPs in the sTMP library, overview. Determination of cleavage sites by amino acid sequencing, consensus-type sequences are X-E/Q-X-D;-G/S, with X being any amino acid
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?
additional information
?
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the substrate cleft is closed in the monomeric zymogen, whereas the cleft is accessible for substrate binding in both dimers, binding structure, overview
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?
additional information
?
-
-
caspase-8 very weakly cleaves nuclear export signal-DEVDR
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?
additional information
?
-
the enzyme is indispensable for Fas-mediated apoptotic signaling
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-
?
additional information
?
-
-
the enzyme is indispensable for Fas-mediated apoptotic signaling
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?
additional information
?
-
-
FLICE is the first in a cascade of ICE-like proteases activated by CD95. Active FLICE is released into the cytosol, where it can activate a cascade of ICE-like proteases
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?
additional information
?
-
-
caspase-8 is dispensable for B-cell development, but its loss in B cells results in attenuated antibody production upon in vivo viral infection. Important role for caspase-8 in maintaining B-cell survival following stimulation of the Toll-like receptor (TLR)2, -3, and -4. In response to TLR4 stimulation, caspase-8 is recruited to a complex containing IKKalphabeta, and its loss results in delayed NFkappaB nuclear translocation and impaired NFkappaB transcriptional activity. Caspase-8 is required forTLRsignaling and in the regulation of NFkappaB function
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?
additional information
?
-
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caspase-8 participates in regulation of the cellular response to infection and injury. It does so by affecting various cellular functions, including cell death, cell proliferation, and induction of inflammation
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?
additional information
?
-
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TLR2- and caspase-8-mediated microglial apoptosis constitutes an autoregulatory mechanism that limits group B Streptococcus-induced overactivation of the innate immune system in the central nervous system
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?
additional information
?
-
-
apoptosis in ischemic hearts occurs through the receptor-mediated extrinsic caspase-8 apoptotic pathway as opposed to the mitochondrial caspase-3 pathway, overview
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?
additional information
?
-
-
apoptotic cell deathin LM3 cells is characterized by the activation of caspase-8, -9 and -3, by an increment in the expression levels of the proapoptotic protein Bax and by the release of cytochrome c to cytosol
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?
additional information
?
-
-
caspase-3 is an initiator caspase. Increased caspase-8 activation is involved in initiation of apoptosis, inhibition of caspase-8 impairs Leptospira interrogans-induced caspase-3 and -6 activation, as well as PARP and lamin A/C cleavage and apoptosis, overview. Leptospira interrogans-induced apoptosis in macrophages is mediated by caspase-3 and -6 activation through a FADDcaspase-8-dependent pathway, independently of mitochondrial cytochrome ccaspase-9-dependent signaling, regulation, overview
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-
?
additional information
?
-
-
caspase-8 acts in apoptosis via the death receptor pathway
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-
?
additional information
?
-
-
caspase-8 is a executioner or downstream caspase. Apoptosis induced by PBOX-21/STI571 results in activation of caspase-8, cleavage of PARP and Bcl-2, upregulation of the pro-apoptotic protein Bim and a downregulation of Bcr-Abl, important role for caspase-8 in the apoptotic pathway, overview
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?
additional information
?
-
-
caspase-8 is a pro-apoptotic caspase, whose expression is increased in the orbito-frontal cortex 14 days after spared nerve injury of the sciatic nerve, prevented by ozone, regulation, overview
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?
additional information
?
-
-
caspase-8 is involved in apoptosis, ischemia upregulates cytoplasmic adaptor protein Fas-associated Fas and Fas-associated death domain, FADD, expression, and increases caspase-8 and -3 activities in ovariectomy female mouse cortex, which are significantly attenuated by estradiol
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?
additional information
?
-
-
mRNA and protein level of caspase-8 is closely related to cell apoptosis by a death ligand/receptor-dependent apoptosis pathway, increased by L-carnitine treatment, overview
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?
additional information
?
-
-
caspase-8 performs self-cleavage to give the processed active dimer. Within the caspase-8/FLIPL heterodimer, caspase-8 prefers to process FLIPL over itself
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?
additional information
?
-
-
pro-caspase-6, linker, is a poor substrate fpr caspase-8
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?
additional information
?
-
-
the substrate cleft is closed in the monomeric zymogen, whereas the cleft is accessible for substrate binding in both dimers, binding structure, overview
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-
?
additional information
?
-
the enzyme is indispensable for Fas-mediated apoptotic signaling
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?
additional information
?
-
-
apoptotic cell deathin LM3 cells is characterized by the activation of caspase-8, -9 and -3, by an increment in the expression levels of the proapoptotic protein Bax and by the release of cytochrome c to cytosol
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?
additional information
?
-
-
apoptosis in ischemic hearts occurs through the receptor-mediated extrinsic caspase-8 apoptotic pathway as opposed to the mitochondrial caspase-3 pathway, overview
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?
additional information
?
-
-
caspase 8 may not only play a role in initiating proapoptotic cascades through activation of downstream caspases but also by amplifying the amount of activated CD95 receptors
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?
additional information
?
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CD95L initiates a rapid caspase 8-dependent endosomal acidification, which triggers ceramide-dependent ROS formation as an upstream event of trafficking of intracellularly stored CD95 to the plasma membrane. A rapid caspase 8 activation in response to CD95L signals to intracellularly stored CD95, which becomes activated and targeted to the plasma membrane
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?
additional information
?
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caspase-8 is involved in apoptosis, but does not require caspase recruitment domain, ARC, which prevents Bax translocation to the mitochondrium and thereby blocks the activation of the mitochondrial apoptotic death pathway in a t-Bid and caspase-8-independent manner, overview
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?
additional information
?
-
-
radiation-induced sensitization of hepatocytes to TNF-alpha-mediated apoptosis additionally requires changes upstream of caspase-8 activation, regulation of caspase-8 and apoptosis in hepatocytes, overview
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?
p28Bap31 + H2O
additional information
-
-
the p20 cleavage product derives from the NH2 terminus of p28
?
p28Bap31 + H2O
additional information
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-
-
the p20 cleavage product derives from the NH2 terminus of p28
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alpha-fodrin + H2O
?
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-
-
-
?
Atg3 protein + H2O
?
-
-
-
?
BH3-only protein Bid + H2O
?
-
-
-
?
BID + H2O
?
-
a 15000 Da C-terminal frament and a 14000 Da N-terminal fragment are generated by caspase-8 cleavage at T58-/-D59. While full-length BID is localized in cytosol, truncated BID translocates to mitochondria and thus transduces apoptotic signals from cytoplasmic membrane to mitochondria. BID is a mediator of mitochondrial damage induced by Casp8
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?
Bid peptide + H2O
truncated Bid peptide + ?
Bid protein + H2O
?
-
-
-
-
?
Bid protein + H2O
cleaved Bid protein
-
i.e. BH3 interacting domain death agonist protein
-
-
?
caspase-3 + H2O
?
-
-
-
-
?
cellular inhibitor of apoptosis 1 + H2O
?
i.e. cIAP-1, TRAIL-induced degradation of cIAP-1 requires caspase 8 activity, and it is, at least in part, due to direct cleavage of cIAP-1 by caspase 8
-
-
?
interleukin-21 + H2O
?
-
-
the CASP8-cleaved form of IL21R does not induce phosphorylation at Tyr705 of STAT3
-
?
parkin + H2O
?
-
cleavage at Asp126-Ser127. Caspase-1 and caspase-8 dependent parkin cleavage in sporadic Parkinsons disease may play an important role in the degenerative process by initiating a vicious circle that leads to the accumulation of toxic parkin substrates, e.g. alpha-synuclein
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-
?
pro-caspase-3 + H2O
caspase-3 + ?
-
caspase-3 is activated through caspase-8 during H2O2-induced apoptosis in HeLa cells
-
-
?
procaspase-3 + H2O
?
-
caspase-8 induces apoptosis by directly activating caspase-3, which in turn causes the characteristic features of apoptosis, including DNA fragmentation and cell death
-
-
?
procaspase-3 + H2O
active caspase-3 + ?
-
direct activation by caspase-8 in type I cells
-
-
?
procaspase-3 + H2O
caspase-3 + ?
procaspase-6 + H2O
caspase-6 + ?
-
cleavage of caspases 3 and 6 by caspase-8 results in apoptosis
-
-
?
procaspase-8 + H2O
caspase-8 + ?
-
caspase-8 is initially synthesized as a single-chain zymogen, procaspase-8, and activated by autocleavage at proteolytic sites Asp126, Asp216, Asp374, and Asp384 after recruitment to DISCs by N-terminal two tandem DEDs of procaspase-8. The proximity-driven dimerization of procaspase-8 is attributable to initiate autocleavage of procaspase-8 involving intra-dimeric and inter-dimeric attack. Dimerized procaspase-8 which achieves enzymatical competency specifically processes one another, while mature caspase-8 can cleave effector caspases and some other substrates. Dramatical conformation changes of the linker region undergo in order to bring cleavage sites, Asp374 and Asp384, to the vicinity of catalytic residue Cys283 from other protomer during dimerization of procaspase-8. Separation of the large and small subunit after intra-dimeric cleavage in the linker region between the large and small subunit renders the linker region between the large subunit and the prodomain of caspase-8 susceptible for the further inter-dimeric cleavage
the C- and N-terminal end, of linker region are released with cleavage at Asp374 and Asp384 before separation of the large and small subunit
-
?
RIPK1 + H2O
?
-
Lys63-linked RIPK1 ubiquitylation is required to render RIPK1 susceptible to caspase 8-mediated cleavage, the mechanism by which RIPK1 signalling is suppressed in this context
-
-
?
vezatin + H2O
?
-
cleaved at Asp655
-
-
?
additional information
?
-
Bid + H2O
tBid + ?
-
Bid is a caspase-8 substrate and that its cleavage can be crucial for CD95-induced apoptosis. Caspase-8-mediated cleavage of Bid into a pro-apoptotically active, truncated form provides the link between death receptor stimulation and mitochondrial apoptotic events
-
-
?
Bid + H2O
tBid + ?
-
i.e. BH3 interacting domain death agonist
-
-
?
Bid peptide + H2O
?
-
-
-
-
?
Bid peptide + H2O
?
-
a specific caspase-8 substrate
-
-
?
Bid peptide + H2O
?
-
CTX III, from crude venom of Naja naja atra, inhibits proliferation of human leukemia K562 cells by G2/M phase arresting and apoptosis which is associated with the activation of caspase-8 and cytochrome c release as well as the p38 and c-Jun N-terminal protein kinase phosphorylation signaling pathway in vitro and in vivo, caspase-8-dependent Bid-Bax pathway, overview
-
-
?
Bid peptide + H2O
truncated Bid peptide + ?
-
-
-
-
?
Bid peptide + H2O
truncated Bid peptide + ?
-
-
-
-
?
CYLD + H2O
CYLDp25 + ?
-
key substrate processed by caspase 8 to block necrosis, CYLD is a key requirement for necrosis
-
-
?
CYLD + H2O
CYLDp25 + ?
-
key substrate processed by caspase 8 to block necrosis, CYLD is a key requirement for necrosis of L929 fibrosarcoma cells
-
-
?
FLIPL protein + H2O
?
-
-
-
-
?
FLIPL protein + H2O
?
-
processing of free FLIPL by caspase-8, FLIPL cleavage increases the recruitment of caspase-8
-
-
?
FLIPL protein + H2O
?
-
processing of free FLIPL by caspase-8, FLIPL cleavage increases the recruitment of caspase-8
-
-
?
procaspase-3 + H2O
caspase-3 + ?
-
-
-
-
?
procaspase-3 + H2O
caspase-3 + ?
-
pro-caspase-3 is a major physiologic target of caspase-8
-
-
?
procaspase-3 + H2O
caspase-3 + ?
-
activation of effector caspase-3 by the initiator caspase-8
-
-
?
procaspase-3 + H2O
caspase-3 + ?
-
cleavage of caspases 3 and 6 by caspase-8 results in apoptosis
-
-
?
procaspase-3 + H2O
caspase-3 + ?
-
in some cells, active caspase-8 is sufficient to activate caspase-3 directly. In other cells, however, caspase-8 indirectly mediates caspase-3 activation by cleaving the proapoptotic Bcl-2 family member Bid, which induces mitochondrial cytochrome c release
-
-
?
procaspase-3 + H2O
caspase-3 + ?
-
procaspase-8 activation in the death-inducing signalling complex, DISC, leads to cleavage of procaspase-3 and engagement of the cellular machinery associated with the type I extrinsic apoptotic pathway
-
-
?
procaspase-3 + H2O
caspase-3 + ?
-
-
-
-
?
procaspase-3 + H2O
caspase-3 + ?
-
in some cells, active caspase-8 is sufficient to activate caspase-3 directly. In other cells, however, caspase-8 indirectly mediates caspase-3 activation by cleaving the proapoptotic Bcl-2 family member Bid, which induces mitochondrial cytochrome c release
-
-
?
additional information
?
-
-
endothelial cell apoptosis induced by bacteria-activated platelets requires caspase-8 and -9 and generation of reactive oxygen species
-
-
?
additional information
?
-
-
caspase-8 is possibly involved in the apoptotic cell death in batch and fed-batch cultures of CHO cells
-
-
?
additional information
?
-
-
role of caspase-8 in the apoptotic signal pathway
-
-
?
additional information
?
-
caspase-8L acts as an inhibitor of caspase-8 by interfering with the binding of caspase-8 to FADD, i.e. Fas-associated protein with death domain, and is involved in the regulation of Fas-mediated apoptosis
-
-
?
additional information
?
-
-
caspase-8L acts as an inhibitor of caspase-8 by interfering with the binding of caspase-8 to FADD, i.e. Fas-associated protein with death domain, and is involved in the regulation of Fas-mediated apoptosis
-
-
?
additional information
?
-
caspase-8 is an initiator enzyme in the Fas-mediated pathway of which the downstream executioner caspase-3 is a physiological target
-
-
?
additional information
?
-
initiator enzyme in apoptosis
-
-
?
additional information
?
-
-
initiator enzyme in apoptosis
-
-
?
additional information
?
-
-
the enzyme acts as apoptosis initiator. Animals deficient in caspase-8 are embryonically lethal at approximately E12.5. Abnormal heart development and vascular hyperemia, EF resistant to Fas, TNF-alpha, and DR3 but exhibit normal sensitivity to UV, etoposide, low serum and staurosporine, death receptor signaling to JNK and NF-kappaB intact
-
-
?
additional information
?
-
-
FLICE binds to the death effector domain of FADD and upon overexpression induces apoptosis that is blocked by the ICE family inhibitors, CrmA and v-VAD-fmk
-
-
?
additional information
?
-
-
FLICE is the first in a cascade of ICE-like proteases activated by CD95. Active FLICE is released into the cytosol, where it can activate a cascade of ICE-like proteases
-
-
?
additional information
?
-
-
the enzyme is responsible for activating a protease cascade after Fas-receptor ligation, leading to cell death. Mch5 is the most upstream protease that receives the activation signal from the Fas-receptor to initiate the apoptotic protease cascade that leads to activation of ICE-like proteases (TX, ICE, and ICE-relIII), Ced-3-like proteases (CPP32, Mch2, Mch3, Mch4 and Mch6) and the ICH-1 protease
-
-
?
additional information
?
-
preferential recruitment of procaspase-8L by the BAP31 complex at the endoplasmic reticulum suggests an additional pathway for regulating initiator caspase-8 during apoptosis
-
-
?
additional information
?
-
-
caspase-8 has a postnatal role in immune activation of native lymphocytes
-
-
?
additional information
?
-
-
caspase-8 occupies an essential and apical position in the fas signaling pathway and suggests that caspase-8 may participate broadly in multiple apoptotic pathways
-
-
?
additional information
?
-
MACH is the most upstream enzymatic component in the Fas/APO-1- and p55-R-induced cell death signaling cascade
-
-
?
additional information
?
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CD95 and TNFR-1 death receptors initiate apoptosis by recruiting FLICE/MACH, which represents the apical triggering member of the protease death cascade and a target for the cell death inhibitor CrmA
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additional information
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the initiator caspase-8 activates other downstream caspases that are incapable of autocatalytic processing and activation
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additional information
?
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the initiator caspase-8 activates other downstream caspases that are incapable of autocatalytic processing and activation
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additional information
?
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caspase-8 inhibits androgen receptor transcriptional activity by disrupting androgen receptor amino-terminal and carboxy-terminal interaction and inhibiting androgen induced androgen receptor nuclear localization
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?
additional information
?
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activation of caspase-8 by glycogen synthase kinase-3 inhibitors can overcome the striking resistance to tumor necrosis factor-related apoptosis-inducing ligand, TRAIL, diplayed by hepatocellular carcinoma cells in contrast to normal heptocytes, overview
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?
additional information
?
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caspase 8 activation induced by C5a leads to cell death if protein synthesis of antiapoptotic proteins are blocked
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additional information
?
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caspase 8 is an initiator caspase that plays an important role in the Fas-Fas ligand pathway
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additional information
?
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caspase family proteases are key proteins in apoptotic signaling pathways, which are activated in both the death receptor-mediated and the mitochondria-mediated apoptosis pathways
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?
additional information
?
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caspase-3 is an initiator caspase. Increased caspase-8 activation is involved in initiation of apoptosis, inhibition of caspase-8 impairs Leptospira interrogans-induced caspase-3 and -6 activation, as well as PARP and lamin A/C cleavage and apoptosis, overview. Leptospira interrogans-induced apoptosis in macrophages is mediated by caspase-3 and -6 activation through a FADD-caspase-8-dependent pathway, independently of mitochondrial cytochrome c-caspase-9-dependent signaling, regulation, overview
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?
additional information
?
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caspase-8 expression is reduced in B-cell chronic lymphocytic leukemia
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?
additional information
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caspase-8 is activated by the death receptor pathway leading to apoptosis. Human herpesvirus HHV-6A-induced apoptosis is associated with activation of caspase-8, caspase-9, and caspase-3, suggesting the involvement of death receptor and mitochondrial signaling pathways, overview. HHV-6 differentially influences the functions of naive T cells and different subsets of memory CD4+ and CD8+ T cells, which in part may be due to differential susceptibility to HHV-6A-induced apoptosis, overview
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additional information
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caspase-8 is activated downstream of the death receptor signaling or via death receptor-independent pathway
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additional information
?
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caspase-8 is an initiator caspase. Procaspase-8 activation is essentially involved in apoptosis induced by selected nutritional free fatty acids, mechanisms, overview
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additional information
?
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caspase-8 is involved in apoptosis in multiple myeloma and is the main initiator caspase in the tumor necrosis factor-related apoptosis-inducing pathway overview. c-FLIPL, is the main endogenous regulator of caspase-8 activation, increases with bortezomib treatment but the combination of Apo2L/TRAIL and bortezomib led to a decrease of both FLIP isoforms, regulation, overview
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-
?
additional information
?
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caspase-8, an initiator caspase, is not involved in MDA-MB-231 apoptotic cell death, overview. Caspase-8 is activated when procaspase-8 is cleaved subsequently from the recruitment of Fas associated protein with death domain, FADD, to the death-effector domain site of procaspase-8 during the oligomerization of death receptor and its ligand
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?
additional information
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caspases 3, 8 and 9 are essential to rhein-induced apoptosis, inhibitors of caspases 3, 8 and 9 are efficiently blocked by rhein-induced apoptosis in TNF-alpha-treated human aortic smooth muscle cells, overview
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-
?
additional information
?
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caspases are a family of aspartate-specific cysteine proteases responsible for the biochemical and morphological changes that occur during the execution phase of apoptosis, model of the intrinsic pathway: caspase-9, the apical caspase, directly processes and activates the effector caspases, caspase-3 and -7, and then active caspase-3, but not caspase-7, processes caspase-2 and -6, and subsequently the activated caspase-6 processes caspase-8 and -10. Caspase-9 but not -8 is required for etoposide-induced processing of caspase-2 and -6. Caspase processing pathways and regulation, overview
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?
additional information
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extrinsic and intrinsic apoptosis induced by equol in human breast cancer MDA-MB cells does not involve caspase-8 activation of receptor-mediated apoptosis, overview
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?
additional information
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Fas ligand, a type II transmembrane protein expressed on the surface of cells, induces apoptotic cell death by binding to its receptor Fas, resulting in recruitment of the Fas-associated death domain protein and caspase 8 zymogens to the receptor and the formation of the death-inducing signalling complex, after which the caspases cascade can be activated. Defects in the Fas/FasL apoptotic signalling pathway provide a survival advantage to cancer cells and may be implicated in tumorigenesis
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?
additional information
?
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Fas-associated death domain-like IL-1beta-converting enzyme inhibitory protein, c-FLIP, can suppress Fas-mediated apoptosis by inhibition of caspase-8 activation. Caspase-8 is active via the death receptor-dependent pathway, or extrinsic pathway, complex formation and mechanism, overview
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-
?
additional information
?
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harmol activates caspase-8 to 334% and induces apoptosis by caspase-8 activation independently on Fas/Fas ligand interaction in human lung carcinoma H-596 cells, but not in H-596, H-226, and A-549 cells
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-
?
additional information
?
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homocysteine-mediated EPC toxicity is due to apoptosis involving caspase-8, cytochrome c release, and caspase-3 activation, overview
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?
additional information
?
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initial activation of caspase-8 causes degradation of glutaredoxin-1, resulting in S-glutathionylation of Fas at cysteine 294, which subsequently enhances binding of FasL, aggregation of Fas, accumulation of Fas in lipid rafts, DISC assembly, and further activation of caspases, causing a propagation of apoptotic cell death. activation of caspases is required for degradation of glutaredoxin-1 and S-glutathionylation of Fas, engagement of Fas causes a rapid activation of caspase-8. Overexpression of Grx1 prevents increases in S-glutathionylation of Fas and attenuates caspase activation and apoptosis in response to receptor ligation. Cleaved caspase-8 and -3 demonstrate an association between active caspases and Grx1 in cells after ligation of Fas, whereas in control cells, these associations are not observed, regulation, overview
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-
?
additional information
?
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interferon regulatory factor 5, IRF-5, promotes apoptosis upon signaling through tumor necrosis factor-related apoptosis-inducing ligand, TRAIL, death receptors, DR. IRF-5 is involved in DR signaling upstream of caspase-8 and induces caspase-8 activation, mechanisms, overview
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?
additional information
?
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involvement of lipid raft aggregates containing recruited Fas/CD95 death receptor, Fas-associated death domain-containing protein, FADD, and procaspase-8 in the induction of apoptosis in human T-cell leukemia Jurkat cells by the antitumor drug edelfosine. Specific inhibition of caspase-8 prevents the apoptotic response triggered by edelfosine
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?
additional information
?
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LRRK2-induced neuronal death is caspase-8-dependent. Fas death domain, FADD, recruits caspase-8 to LRRK2. FADD transduces death signals by binding to ligand-activated Fas via its DD and recruiting and activating caspase-8 via its death-effector domain, DED. The Parkinson disease protein leucine-rich repeat kinase 2 transduces death signals via Fas-associated protein with death domain and caspase-8 in a cellular model of neurodegeneration. In primary neuronal culture LRRK2-mediated neurodegeneration is prevented by the functional inhibition of FADD or depletion of caspase-8, two key elements of the extrinsic cell death pathway, overview
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?
additional information
?
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methotrexate-induced apoptosis does not involve activation of caspase-8, but of caspase-9, overview. Caspase-8 is recruited to an apoptosis-inducing signaling complex when apoptotic receptors are oligomerized after binding of specific ligands. Active caspase-8 can either act directly on downstream executioner caspases, or indirectly on mitochondria
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-
?
additional information
?
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netrin-1 siRNA-induced H-358 cell death is mediated by caspase-3 and -9 activities, but not by caspase-8 activity
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?
additional information
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stem-cell-like glioma cells are resistant to tumour necrosis factor -related apoptosis-inducing ligand, TRAIL/Apo2L and exhibit down-regulation of caspase-8 by promoter methylation
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?
additional information
?
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The cysteine protease caspase-8 plays an essential role in apoptosis induced by death receptors, caspase-8 mediates mitochondrial release of pro-apoptotic proteins in a manner independent of its proteolytic activity in apoptosis induced by the protein synthesis inhibitor acetoxycycloheximide in human leukemia Jurkat cells. Bid is cleaved not by caspase-8 but by other caspases in Ac-CHX-treated cells and is not involved in mitochondrial release of proapoptotic proteins
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?
additional information
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Arg-Gly-Asp-Ser directly and specifically binds pro-caspase-8
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?
additional information
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caspase-4 activation requires the action of upstream initiator components such as caspase-8
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?
additional information
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FADD-like interleukin-1beta-converting enzyme-inhibitory protein is an antagonist of caspases-8
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?
additional information
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caspase-8 is involved in activation of acid sphingomyelinase induced by TNF, but caspase-8 does not display firm association neither with caspase-7 nor with A-SMase, overview. Direct binding of caspase-8 to TNF-R1 on internalized receptosomes
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-
?
additional information
?
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caspase-8 performs self-cleavage to give the processed active dimer. Within the caspase-8/FLIPL heterodimer, caspase-8 prefers to process FLIPL over itself
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?
additional information
?
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the enzyme is indispensable for Fas-mediated apoptotic signaling
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?
additional information
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the enzyme is indispensable for Fas-mediated apoptotic signaling
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?
additional information
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FLICE is the first in a cascade of ICE-like proteases activated by CD95. Active FLICE is released into the cytosol, where it can activate a cascade of ICE-like proteases
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?
additional information
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caspase-8 is dispensable for B-cell development, but its loss in B cells results in attenuated antibody production upon in vivo viral infection. Important role for caspase-8 in maintaining B-cell survival following stimulation of the Toll-like receptor (TLR)2, -3, and -4. In response to TLR4 stimulation, caspase-8 is recruited to a complex containing IKKalphabeta, and its loss results in delayed NFkappaB nuclear translocation and impaired NFkappaB transcriptional activity. Caspase-8 is required forTLRsignaling and in the regulation of NFkappaB function
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?
additional information
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caspase-8 participates in regulation of the cellular response to infection and injury. It does so by affecting various cellular functions, including cell death, cell proliferation, and induction of inflammation
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?
additional information
?
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TLR2- and caspase-8-mediated microglial apoptosis constitutes an autoregulatory mechanism that limits group B Streptococcus-induced overactivation of the innate immune system in the central nervous system
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?
additional information
?
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-
apoptosis in ischemic hearts occurs through the receptor-mediated extrinsic caspase-8 apoptotic pathway as opposed to the mitochondrial caspase-3 pathway, overview
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-
?
additional information
?
-
-
apoptotic cell deathin LM3 cells is characterized by the activation of caspase-8, -9 and -3, by an increment in the expression levels of the proapoptotic protein Bax and by the release of cytochrome c to cytosol
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-
?
additional information
?
-
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caspase-3 is an initiator caspase. Increased caspase-8 activation is involved in initiation of apoptosis, inhibition of caspase-8 impairs Leptospira interrogans-induced caspase-3 and -6 activation, as well as PARP and lamin A/C cleavage and apoptosis, overview. Leptospira interrogans-induced apoptosis in macrophages is mediated by caspase-3 and -6 activation through a FADDcaspase-8-dependent pathway, independently of mitochondrial cytochrome ccaspase-9-dependent signaling, regulation, overview
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?
additional information
?
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-
caspase-8 acts in apoptosis via the death receptor pathway
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?
additional information
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caspase-8 is a executioner or downstream caspase. Apoptosis induced by PBOX-21/STI571 results in activation of caspase-8, cleavage of PARP and Bcl-2, upregulation of the pro-apoptotic protein Bim and a downregulation of Bcr-Abl, important role for caspase-8 in the apoptotic pathway, overview
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?
additional information
?
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caspase-8 is a pro-apoptotic caspase, whose expression is increased in the orbito-frontal cortex 14 days after spared nerve injury of the sciatic nerve, prevented by ozone, regulation, overview
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?
additional information
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caspase-8 is involved in apoptosis, ischemia upregulates cytoplasmic adaptor protein Fas-associated Fas and Fas-associated death domain, FADD, expression, and increases caspase-8 and -3 activities in ovariectomy female mouse cortex, which are significantly attenuated by estradiol
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?
additional information
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mRNA and protein level of caspase-8 is closely related to cell apoptosis by a death ligand/receptor-dependent apoptosis pathway, increased by L-carnitine treatment, overview
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?
additional information
?
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caspase-8 performs self-cleavage to give the processed active dimer. Within the caspase-8/FLIPL heterodimer, caspase-8 prefers to process FLIPL over itself
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-
?
additional information
?
-
the enzyme is indispensable for Fas-mediated apoptotic signaling
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?
additional information
?
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apoptotic cell deathin LM3 cells is characterized by the activation of caspase-8, -9 and -3, by an increment in the expression levels of the proapoptotic protein Bax and by the release of cytochrome c to cytosol
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?
additional information
?
-
-
apoptosis in ischemic hearts occurs through the receptor-mediated extrinsic caspase-8 apoptotic pathway as opposed to the mitochondrial caspase-3 pathway, overview
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?
additional information
?
-
-
caspase 8 may not only play a role in initiating proapoptotic cascades through activation of downstream caspases but also by amplifying the amount of activated CD95 receptors
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?
additional information
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CD95L initiates a rapid caspase 8-dependent endosomal acidification, which triggers ceramide-dependent ROS formation as an upstream event of trafficking of intracellularly stored CD95 to the plasma membrane. A rapid caspase 8 activation in response to CD95L signals to intracellularly stored CD95, which becomes activated and targeted to the plasma membrane
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?
additional information
?
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caspase-8 is involved in apoptosis, but does not require caspase recruitment domain, ARC, which prevents Bax translocation to the mitochondrium and thereby blocks the activation of the mitochondrial apoptotic death pathway in a t-Bid and caspase-8-independent manner, overview
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additional information
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radiation-induced sensitization of hepatocytes to TNF-alpha-mediated apoptosis additionally requires changes upstream of caspase-8 activation, regulation of caspase-8 and apoptosis in hepatocytes, overview
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(3S)-3-([[2-(3-carboxypropyl)-1,3-dioxo-8-(2-phenylethyl)-2,3,5,8-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazin-5-yl]carbonyl]amino)-5-[(2,6-dichlorobenzoyl)oxy]-4-oxopentanoic acid
-
-
(3S)-3-([[2-(3-carboxypropyl)-1,3-dioxo-8-(pyridin-3-yl)-2,3,5,8-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazin-5-yl]carbonyl]amino)-5-[(2,6-dichlorobenzoyl)oxy]-4-oxopentanoic acid
-
-
(3S)-3-([[2-(3-carboxypropyl)-1,3-dioxo-8-[2-[(thiophen-2-ylacetyl)amino]ethyl]-2,3,5,8-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazin-5-yl]carbonyl]amino)-5-[(2,6-dichlorobenzoyl)oxy]-4-oxopentanoic acid
-
-
(3S)-3-([[2-(3-carboxypropyl)-8-(2-[[(4-chlorophenyl)acetyl]amino]ethyl)-1,3-dioxo-2,3,5,8-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazin-5-yl]carbonyl]amino)-5-[(2,6-dichlorobenzoyl)oxy]-4-oxopentanoic acid
-
compound-4 is binding to caspase-8 in a pocket far from the active site
(3S)-3-([[2-[2-[(1H-benzimidazol-6-ylcarbonyl)amino]ethyl]-7-(cyclohexylmethyl)-1,3-dioxo-2,3,5,8-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazin-5-yl]carbonyl]amino)-5-[(2,6-dichlorobenzoyl)oxy]-4-oxopentanoic acid
-
-
(3S)-3-([[2-[2-[(cyclohexylcarbonyl)amino]ethyl]-7-(cyclohexylmethyl)-1,3-dioxo-2,3,5,8-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazin-5-yl]carbonyl]amino)-5-[(2,6-dichlorobenzoyl)oxy]-4-oxopentanoic acid
-
-
(3S)-3-[[(2-[4-carboxy-2-[(phenylacetyl)amino]butyl]-1,3-dioxo-2,3,5,7,8,9,10,10a-octahydro-1H-[1,2,4]triazolo[1,2-a]cinnolin-5-yl)carbonyl]amino]-5-[(2,6-dichlorobenzoyl)oxy]-4-oxopentanoic acid
-
-
(3S)-5-[(2,6-dichlorobenzoyl)oxy]-3-[([1,3-dioxo-2-[2-(1H-tetrazol-5-yl)ethyl]-2,3,5,7,8,9,10,10a-octahydro-1H-[1,2,4]triazolo[1,2-a]cinnolin-5-yl]carbonyl)amino]-4-oxopentanoic acid
-
-
2'-nitroflavone
-
inhibits caspases and tumor cell growth in diverse tissues, overview
4-[5-([(3S)-1-[(2,6-dichlorobenzoyl)oxy]-2,5-dioxohexan-3-yl]carbamoyl)-1,3-dioxo-8-(thiophen-2-yl)-5,8-dihydro-1H-[1,2,4]triazolo[1,2-a]pyridazin-2(3H)-yl]butanoic acid
-
-
acetyl-Asp-Glu-Val-Asp-al
-
-
acetyl-Ile-Glu-Thr-Asp-al
-
-
acetyl-Leu-Glu-His-Asp-al
-
-
acetyl-Val-Asp-Val-Ala-Asp-al
-
0.01 mM, 80% inhibition
benzyloxycarbonyl-DEVD-aldehyde
the inhibitor interacts favourably with the enzyme in subsite S4
benzyloxycarbonyl-IETD-fluoromethyl ketone
-
benzyloxycarbonyl-IETD-fluoromethylketone
benzyloxycarbonyl-Ile-Glu-Thr-Asp-fluoromethylketone
benzyloxycarbonyl-L-Asp-2,6-dichlorobenzoyloxymethylketone
-
pan-caspase inhibitor
benzyloxycarbonyl-LEHD-fluoromethylketone
-
a caspase-9 inhibitor, partial inhibition of caspase-8 activation in lung carcinoma cells
benzyloxycarbonyl-Leu-Glu-His-Asp-fluoromethylketone
-
-
benzyloxycarbonyl-VAD-fluoromethylketone
benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone
-
benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone
-
t1/2 at 0.001 mM: 2.5 s
benzyloxycarbonyl-Val-Asp-Val-Ala-Asp-fluoromethylketone
-
-
benzyloxycarbonyl-valyl-alanyl-aspartic acid (O-methyl)-fluoro-methylketone
-
biotin-conjugated valine-alanine-aspartate-fluoromethylketone
-
carboxyfluorescein-labeled-LETD-fluoromethylketone
-
-
carboxyfluorescein-LETD-fluoromethylketone
-
-
Cbz-Val-Ala-Asp[O-methyl]-fluoromethylketone
-
pan-caspase inhibitor
cellular FLICE inhibitory protein
-
-
-
Fas-associated death domain-like interleukin 1-converting enzyme-inhibitory proteins
FLIPs, natural inhibitor
-
IETD-CHO
-
specific caspase-8 inhibitor
IETD-fluoromethyl ketone
-
a caspase-8-specific inhibitor
IETD-fluoromethylketone
-
-
Ile-Glu-Thr-Asp-[O-methyl]-fluoromethylketone
-
-
N-benzyloxycarbonyl-VAD-fluoromethyl ketone
-
a general caspase inhibitor
N-benzyloxycarbonyl-VAD-fluoromethylketone
-
an irreversible caspase inhibitor
N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone
-
N-carbobenzyloxy-IETD-fluoromethyl ketone
N-carbobenzyloxy-Ile-Glu(OMe)-Thr-Asp(OMe) fluoromethyl ketone
-
caspase-8 inhibition inhibits apoptosis
N-carbobenzyloxy-VAD-fluoromethyl ketone
p35
-
p35 protein from baculovirus inhibits in the active site through a covalent thioester linkage to p35. The p35 protein undergoes dramatic conformational changes on cleavage by the caspase. The repositioning of the amino terminus of p35 into the active site of the caspase eliminates solvent accessibility of the catalytic dyad
-
Q-VD-OPH
pan-caspase inhibitor
tert-butyloxycarbonyl-IETD-aldehyde
-
triptolide
-
a diterpenoid triepoxide derived from the herb Tripterygium wilfordii that is used as a natural medicine in China, activates caspase-8 4-6fold in pituitary adenoma cancer cells within 2 days, overview
Z-IETD-fluoromethyl ketone
-
Z-IETD-fluoromethylketone
Z-VAD
pan-caspase inhibitor
Z-Val-Ala-Asp(OCH3)-fluoromethylketone
-
Ac-IETD-CHO
-
-
acetyl-IETD-aldehyde
-
-
acetyl-IETD-aldehyde
IC50: 50 nM, covalently modifies the active site C360
benzyloxycarbonyl-IETD-fluoromethylketone
-
specific caspase-8 inhibitor
benzyloxycarbonyl-IETD-fluoromethylketone
-
specific caspase-8 inhibitor
benzyloxycarbonyl-IETD-fluoromethylketone
-
caspase-8 inhibitor
benzyloxycarbonyl-IETD-fluoromethylketone
-
-
benzyloxycarbonyl-IETD-fluoromethylketone
-
specific inhibitor of caspase-8
benzyloxycarbonyl-IETD-fluoromethylketone
-
caspase 8 inhibitor
benzyloxycarbonyl-IETD-fluoromethylketone
-
specific caspase-8 inhibitor
benzyloxycarbonyl-IETD-fluoromethylketone
-
-
benzyloxycarbonyl-Ile-Glu-Thr-Asp-fluoromethylketone
-
-
benzyloxycarbonyl-Ile-Glu-Thr-Asp-fluoromethylketone
-
-
benzyloxycarbonyl-VAD-fluoromethylketone
-
pan-caspase inhibitor
benzyloxycarbonyl-VAD-fluoromethylketone
-
pan-caspase inhibitor
benzyloxycarbonyl-VAD-fluoromethylketone
-
-
benzyloxycarbonyl-VAD-fluoromethylketone
-
pan-caspase inhibitor
benzyloxycarbonyl-VAD-fluoromethylketone
-
multi-caspase inhibitor
benzyloxycarbonyl-VAD-fluoromethylketone
-
pan-caspase inhibitor
cFLIP
-
a caspase 8 homologue, FLICE-inhibitory protein, acts as a competitive inhibitor to caspase 8 by blocking caspase 8 binding to the death induced signaling complex
-
cFLIP
-
high levels of cFLIP can abrogate caspase-8 activation at the DISC
-
cowpox serpin CrmA
-
Ki below 0.34 nM
-
cowpox serpin CrmA
CrmA, a pox virus-encoded serpin attenuates the ability of FLICE to activate downstrean caspases
-
cowpox serpin CrmA
-
potent inhibitor
-
CrmA
-
-
CrmA
-
inhibits caspase 8, while mutant CrmAD303A is unable to prevent cleavage of CYLD
-
CrmA
-
inhibits caspase 8, while mutant CrmAD303A is unable to prevent cleavage of CYLD
-
FLIPL protein
-
inhibits cleavage of Bid
-
FLIPL protein
-
i.e. FLICE-like inhibitory protein long, inhibits apoptotic caspase 8 activation. FLIP is homologous to caspase 8 but lacks catalytic residues. FLIP forms a heterodimer with caspase 8, which prevents apoptosis induction. Dynamic ubiquitylation is at least partially responsible for controlling the activation of caspase 8 by FLIPL
-
N-carbobenzyloxy-IETD-fluoromethyl ketone
-
a caspase-8 inhibitor, inhibition of caspase-8 activation in lung carcinoma cells
N-carbobenzyloxy-IETD-fluoromethyl ketone
-
a specific caspase-8 inhibitor
N-carbobenzyloxy-IETD-fluoromethyl ketone
-
effects on the activation of caspase-8 through cell infection with Leptospira interrogans
N-carbobenzyloxy-IETD-fluoromethyl ketone
-
a caspase-8-specific inhibitor
N-carbobenzyloxy-IETD-fluoromethyl ketone
-
a caspase-8-specific inhibitor, that efficiently reduces rhein-induced apoptosis by 77% at 0.01 mM resulting in 17% apoptotic cells
N-carbobenzyloxy-IETD-fluoromethyl ketone
-
a caspase-8 imhibitor, reduces the apoptotic rate in LAMA84 cells by about 50%, and prevents pro-caspase-8 cleavage
N-carbobenzyloxy-IETD-fluoromethyl ketone
-
effects on the activation of caspase-8 through cell infection with Leptospira interrogans
N-carbobenzyloxy-VAD-fluoromethyl ketone
-
a pan-caspase inhibitor
N-carbobenzyloxy-VAD-fluoromethyl ketone
-
the pan-caspase inhibitor prevents the sensitizing effects of lithium and SB-415286
N-carbobenzyloxy-VAD-fluoromethyl ketone
-
-
N-carbobenzyloxy-VAD-fluoromethyl ketone
-
a general caspase inhibitor, that effectively blocks FasL-induced cleavage of caspase-8 and completely prevents FasL-induced degradation of Grx1
N-carbobenzyloxy-VAD-fluoromethyl ketone
-
a general caspase inhibitor
N-carbobenzyloxy-VAD-fluoromethyl ketone
-
a general caspase inhibitor
Z-EVD-chloromethylketone
-
-
Z-EVD-chloromethylketone
-
-
Z-IETD
-
Z-IETD
caspase-8-specific inhibitor
Z-IETD-fluoromethylketone
-
a strong caspase-8 specific inhibitor, moderate inhibitory role of Z-IETD-fluoromethylketone on the H2O2-induced cell number decrease
Z-IETD-fluoromethylketone
caspase 8 inhibitor
Z-IETD-fluoromethylketone
-
-
Z-VAD-fluoromethylketone
-
-
Z-VAD-fluoromethylketone
-
i.e. benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone
Z-VAD-fluoromethylketone
-
-
additional information
-
inhibition of caspase-8 enhances the viability of the CHO cells in both batch and fed-batch suspension cultures
-
additional information
-
xanthorrhizol does not affect caspase-8
-
additional information
-
nitric oxide synthase activity in leukocytes seems to inhibit Fas-induced apoptosis preventing caspase-8 activation
-
additional information
-
poly(ADP-ribose) polymerase 1, PARP-1, suppression does not affect procaspase-8 expression, overview
-
additional information
-
structure-based drug design approach, synthesis of beta-strand urazole ring-containing irreversible peptidomimetic compounds. Z-VAD-fluoromethylketone and the peptidomimetic inhibitors inhibit caspase-8 via a three-step kinetic mechanism, i.e. a rapid equilibrium step, a slow-binding reversible step, and an extremely slow inactivation step, caspase-inhibitor interactions, overview. One of the caspase-8 structures also shows binding at a secondary, allosteric site, providing a possible route to the development of noncovalent small molecule modulators of caspase activity
-
additional information
-
both the caspase 3 and 9 inhibitors Z-DEVD-fluoromethylketone and Z-LEHD-fluoromethylketone fail to inhibit the activation of caspase 8
-
additional information
-
as a potential cell migration/adhesion factor, c-src blocks activation of caspase-8 through phosphorylating caspase-8 at Tyr380
-
additional information
activity decreases in aged oocytes, compared to young ones
-
additional information
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activity decreases in aged oocytes, compared to young ones
-
additional information
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interleukin-1 does not downregulate caspase-8 expression, but reduces apoptosis within the gastrointestinal crypts
-
additional information
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high doses of ozone inhibit caspase-8 overexpression
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6'-benzyloxy-4-bromo-2'-hydroxychalcone
compound displays potent cytotoxic properties against human leukaemia cells U-937, HL-60, K-562, NALM-6 and MOLT-3. Application results in significant activation of caspase-8 after 24 h of treatment
actinomycin D
-
significantly activates caspase-8
cellular FLIP long form
-
-
complement factor 5a
-
increases caspase-8 activity and expression level of procaspase-8, and increases caspase 8 homologue FLICE-inhibitory protein, cFLIP, activation, C5a stimulation initiated cFLIP cleavage, which increased the 43 kDa active fragment, overview
-
edelfosine
-
i.e. 1-O-octadecyl-2-O-methyl-racglycero-3-phosphocholine, an anti-tumor drug, induces activation of procaspase-8 in T-cell leukemia, specific inhibition of caspase-8 prevents the apoptotic response triggered by edelfosine, overview. The compound induces the generation of the so-called death-inducing signaling complex, DISC, made up of Fas/CD95, FADD, and procaspase-8, in lipid rafts
Fas death domain
-
FADD, activating caspase-8 via its death-effector domain, DED. FADD dimerizes on binding to Fas, a crucial event that greatly enhances both the FADD-Fas interaction and caspase-8 activation
-
Fas-associated death domain protein-like interleukin-1-beta-converting enzyme-like inhibitory protein, long form
FLIP L, results in a heterodimeric enzyme
-
harmol
-
i.e. 1-methyl-9H-beta-carbolin-7-ol, a natural beta-carboline plant alkaloid, induces caspase-8 activation
homocysteine
-
induces the enzyme activation 3.5fold in endothelial progenitor cells at 0.2 mM
interferon-alpha
increases caspase-8 transcription
-
lithium/SB-415286
-
two GSK-3 inhibitor, enhance caspase-8 activity in hepatoma cells, but not in healthy hepatocyte, and increase the sensitivity of the cells to tumor necrosis factor-related apoptosis-inducing ligand, i.e. TRAIL, or CH-11, a CD95 agonistic antibody, which leads to increased apoptosis, the agents have no effect alone, mechanism, overview, 1.5-2.1fold activation of CH-11-induced apoptosis at 20 mM LiCl and 0.025 mM SB-415286
NPI-0052
-
the chemotherapeutic agent, i.e. salinosporamide A, a proteasome inhibitor, activates the caspase-8-dependent apoptosis pathway in multiple myeloma cells, it potentiates the apoptosis induced by TNF-alpha, bortezomib, and thalidomide, regulation, overview
radiation
increases caspase-8 expression and activity
-
resveratrol
-
causes activation of caspase-8, which in turn results in modulation of mitochondrial apoptotic machinery to promote apoptosis of rheumatoid arthritis fibroblast-like synoviocytes
Sodium citrate
enhances activity
TNF-alpha/irradiation
-
leads to an increase of caspase-8 activity up to 3.2fold within 24 h and up to 4.4fold within 48 h after irradiation, administration of TNF-alpha to non-irradiated hepatocytes does not lead to an increased activity of caspase-8
-
Tumor necrosis factor alpha
-
-
tumor necrosis factor-alpha
increases activity after 24 h exposure
-
CD95
-
FLICE is the first in a cascade of ICE-like proteases activated by CD95. This activation requires a functional CD95 disc
-
CD95
-
FLICE is the first in a cascade of ICE-like proteases activated by CD95. This activation requires a functional CD95 disc
-
FLIPL protein
-
a catalytically defective caspase-8 paralogue, can interact with caspase-8 to activate its catalytic function
-
FLIPL protein
-
a catalytically defective caspase-8 paralogue, can interact with caspase-8 to activate its catalytic function
-
additional information
combination of interferon-alpha/TRAIL increases activity significantly
-
additional information
-
combination of interferon-alpha/TRAIL increases activity significantly
-
additional information
dimerization
-
additional information
-
alpha-trifluoromethyl acyloins TF2 and TF3, i.e. CF3CH(OH)COPh and CF3CH(OH)COCH2Ph, fail to activate caspase-8 in both HSC-2 and HSC-4 cells during 4-24 hours treatment, however, TF2 and TF3 induce apoptotic cell death in human submandibular gland carcinoma cells
-
additional information
-
caspase-8 is activated by homodimerization, which also leads to autoproteolytic processing of the enzyme into multiple smaller species
-
additional information
-
caspase-8 is activated downstream of the death receptor signaling or via death receptor-independent pathway
-
additional information
-
CTX III, from crude venom of Naja naja atra, induces the activation of caspase-8 as part of the caspase-8-dependent Bid-Bax pathway, overview
-
additional information
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engagement of Fas causes a rapid activation of caspase-8, induction of caspase-8 by Fas ligand, FasL, overview. Increased S-glutathionylation of Fas, caspase-8 activity, and cell death in cells lacking Grx1
-
additional information
-
Leptospira interrogans induces apoptosis in macrophages and hepatocytes via caspase-8- and caspase-3-dependent pathways
-
additional information
-
no activation by methotrexate
-
additional information
-
no activation of caspase-8 by equol
-
additional information
-
no enzyme activation by natural beta-carboline alkaloids harmalol, harmine, and harmaline, i.e. 1-methyl-4,9-dihydro-3H-beta-carbolin-7-ol, 7-methoxy-1-methyl-9H-beta-carboline, and 7-methoxy-1-methyl-4,9-dihydro-3H-beta-carboline, respectively
-
additional information
-
obatoclax enhances TRAIL-mediated apoptosis, which is accompanied by activation of caspase-8, -9, and -3 and cleavage of Bid. A feedback amplification loop mediated by caspase-3 may contribute to activation of caspase-8 and Bid, overview
-
additional information
-
procaspase-8 is cleaved to 41 and 43 kDA fragments for activation, overview
-
additional information
-
rosiglitazone, i.e. BRL, induces procaspase-8 cleavage and activation to caspase-8 leading to apoptosis in breast cancer cells. Rosiglitazone transactivates the FasL promoter gene in a peroxisome proliferator-activated receptor gamma PPARgamma-dependent manner
-
additional information
-
the antioxidant 7,8-diacetoxy-4-methylcoumarin, DAMC, and its thiocoumarin derivative 7,8-diacetoxy-4-methylthiocoumarin, DAMTC, induce apoptosis by activating caspase-9 and caspase-3 without affecting the activity of caspase-8
-
additional information
-
the interferon regulatory factor 5, IRF-5, induces caspase-8 activation
-
additional information
-
TNF-related apoptosis-inducing ligand and etoposide induce caspase-8 activation, which is inhibited by caspase inhibitor N-carbobenzyloxy-VAD-fluoromethyl ketone, but not by M-791
-
additional information
-
tumor necrosis factor-related apoptosis-inducing ligand, i.e. Apo2L/TRAIL, is a death messenger that induces apoptosis in many types of human hematological neoplasia including multiple myeloma by inducing activation of caspase-8 and caspase-3. Bortezomib enhances the activating effect on capsase-8
-
additional information
-
xanthorrhizol does not affect caspase-8
-
additional information
-
caspase-8 integration into cardiolipin-rich domains of the outer mitochondrial membrane results in full activation of this caspase which can then directly access and cleave its substrate Bid
-
additional information
-
procaspase-8 activation via self-cleavage, overview
-
additional information
-
tumor necrosis factor alpha stimulation results in a caspase-8-dependent Her-2 cleavage in MCF-7 breast adenocarcinoma cells defective for nuclear factor kappaB activation
-
additional information
infection with Trypanosoma cruzi
-
additional information
-
infection with Trypanosoma cruzi
-
additional information
-
active caspase-8 is upregulated under irradiation stress, and interleukin-1 does not prevent it when used in pretreatment, overview
-
additional information
-
caspase-8 expression is increased in the orbito-frontal cortex 14 days after spared nerve injury of the sciatic nerve, prevented by ozone
-
additional information
-
caspase-8 expression is induced by Fas, and L-carnitine induces Fas and caspase-8
-
additional information
-
caspase-8 is induced in brain by cerebral ischemia. Upon activation, the cytoplasmic adaptor protein Fas-associated death domain associates with the death domain of Fas, followed by recruitment and activation of caspase-8
-
additional information
-
dexamethasone induces the enzyme in thymus
-
additional information
-
Leptospira interrogans induces apoptosis in macrophages and hepatocytes via caspase-8- and caspase-3-dependent pathways
-
additional information
-
no induction or activation of caspase-8 by cordycepin in MA-10 mouse Leydig tumor cells, overview
-
additional information
-
PBOX-21/STI571 induces activation of caspase-8 leading to aopotosis
-
additional information
-
caspase-8 activation involves dimerization and subsequent interdomain autoprocessing of caspase-8 zymogens, mechanism, overview. The inactive caspase-8 paralogue FLIPL is able to activate caspase-8 by heterodimerization
-
additional information
-
irradiation induces TNF-alpha-mediated activation of caspase-8, and apoptosis in hepatocytes. Apoptosis induction is prevented by IkappaB antisense oligonucleotides mediated by suppression of caspases-9 and -3 activation but not of caspase-8 activation, overview
-
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evolution
-
caspase-3 is an executioner caspase
evolution
-
initiator and executioner caspases, the pro-apoptotic members of the caspase family are subdivided in the initiators of apoptosis and the executioners of apoptosis. Caspase-18 and the ancestor of -8 and -10 called caspase-810 in this schematic are still found in fishes. Later on in evolution, caspase-8 and -10 branched off from caspase-810
evolution
-
initiator and executioner caspases, the pro-apoptotic members of the caspase family are subdivided in the initiators of apoptosis, i.e. caspases-8, -9 and -10 in humans, and the executioners of apoptosis, caspase-3, -6 and -7, phylogenetic tree of all the human caspases, overview. The initiators have a relatively large N-terminal dimerization domain, either a death effector domain, caspases-8 and -10, or a structurally related caspase recruitment domain, caspase-9. Caspase-18 and the ancestor of -8 and -10 called caspase-810 in this schematic are still found in fishes. Later on in evolution, caspase-8 and -10 branched off from caspase-810
malfunction
-
caspase-8 inhibition decreases biofilm cell survival
malfunction
-
caspase-8 inhibition decreases biofilm cell survival
malfunction
-
caspase-8 inhibition decreases biofilm cell survival
malfunction
-
depletion of caspase-8 decreases endogenous amyloid beta-protein production
malfunction
-
silencing of caspase 8 gene is a key factor controlling the outcome of neonatal astrocytes upon Fas engagement, restoration of caspase 8 expression triggers apoptotic cell death in primary neonatal astrocytes
malfunction
caspase 8 knockdown stabilizes both cellular inhibitor of apoptosis 1, cIAP-1, and X-linked IAP, XIAP
malfunction
-
cells lacking in caspase-8 show reduced adhesion to fibronectin with concomitant reduction in adhesion-induced ERK 1/2 activation, these effects can be restored upon reexpression of either the wild-type or catalytically inactive point mutant protein, implying caspase-8 is involved to promote cell adhesion and adhesion-induced ERK 1/2 activation independently of its catalytical activity
malfunction
-
developmental abnormalities of caspase-8-deficient mice
malfunction
-
in p62-deficient cancer cells caspase-8 activity and apoptosis are diminished, yet not abrogated
malfunction
-
loss of caspase 8 prevents CYLD degradation, resulting in necrotic death. Mutation of the caspase 8 processing site on the substrate converts a pro-survival response to necrotic death without the need for caspase 8 inhibition
malfunction
-
loss of caspase 8 prevents CYLD degradation, resulting in necrotic death. Mutation of the caspase 8 processing site on the substrate converts a pro-survival response to necrotic death without the need for caspase 8 inhibition
malfunction
-
mice deficient in caspase-8 in basal epidermal keratinocytes suffer from chronic skin inflammation, as an apparent consequence of IRF3 hyper-activation. Catalytically active caspase-8 is required to rescue the lymphocyte development in caspase-8 deficient mice. The developmental phenotype observed in the caspase-8 knockout mouse is shared with both the FLIPL knockout and the FADD knockout
malfunction
-
no change in A-SMase activity in caspase-8-deficient cells. Retransfection of caspase-8-deficient Jurkat cells with an expression plasmid for caspase-8 restores the ability of the transfected cells to respond to TNF stimulation by increased A-SMase activity. Caspase-8-deficient Jurkat cells are almost completely resistant to TNF/CHX treatment
malfunction
-
proliferative defects of caspase 8-deficient T cells and B cells. Caspase-8 deficiency causes programmed necrotic cell death
malfunction
caspase-8 is coupled with the regulation of various neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Huntington's disease and dentatorubral pallidoluysian atrophy
malfunction
failure to express caspase-8 has no effect on the life-span of dendritic cells but instead leads to an enhanced intrinsic activation and subsequently more mature and autoreactive lymphocytes. Mice with conditional deletion of caspase-8 in DCs develop a chronic systemic autoimmune disease
malfunction
-
caspase-8 inhibition decreases biofilm cell survival
-
malfunction
-
caspase-8 inhibition decreases biofilm cell survival
-
malfunction
-
caspase-8 inhibition decreases biofilm cell survival
-
metabolism
-
caspase-8 of the extrinsic pathway is able to activate upstream mediators of the intrinsic apoptotic pathway
metabolism
-
activation of caspase 8 is upstream of caspase 3 activation
metabolism
-
caspase-8 and Bid are the known procurers of the death signal leading from death receptor stimulation to permeabilisation of the outer mitochondrial membrane in the apoptotic pathway, regulation of caspase-8 and Bid function and activation, overview
metabolism
-
mathematical modeling of CD95 DISC-mediated MAPK activation and apoptosis, overview. Quantitative dynamics of DED proteins, procaspase-8, and c-FLIP, which lead to caspase-8 activation and induction of apoptotic and non-apoptotic signaling pathways
metabolism
-
recruitment of caspase 8 and FLIP to a RIPK1-containing complex determines cell fate, overview
metabolism
-
the interaction of phosphorylated caspase-8 with regulatory subunit, p85alpha, of phosphatidylinositol-3-OH kinase enhances Rac activation to promote cell migration, requiring Tyr380 and phosphorylation by c-src
metabolism
model of caspase 8 activation. Upon apoptosis induction triggered by interaction of the death ligand to the trimeric death receptor, adaptor FADD (Fas-associated protein with death domain ) is recruited to the death receptor via a death domain DD-DD interaction. FADD recruited at cell surface can recruit caspase-8 via a DED-DED interaction, leading to procaspase-8 proximity to meet another procaspase-8. Closely located FL motif on DED2 causes domain swapping and dimerization of procaspase-8. The dimerization via tandem DED domain swapping causes the proximity-mediated self-activation of caspase-8
physiological function
-
activation of caspase 8 is involved in Fas-induced apoptosis in neonatal astrocytes
physiological function
-
apoptosis is mediated with caspase-8 activation
physiological function
-
caspase 8 is a key molecule of apoptosis in hepatocellular carcinoma. Methylation of caspase 8 and positive expression of its gene product is significantly correlated with high apoptotic indices
physiological function
-
caspase 8 is involved in apoptosis, trophoblast differentiation process, regulation of inflammatory processes, lymphocyte proliferation, cell migration, and cell differentiation with or without enucleation
physiological function
-
caspase-8 is involved in the presenilin1/gamma-secretase-dependent cleavage of amyloid precursor protein after the induction of apoptosis
physiological function
-
caspase-8 is not essential in goniothalamin-induced apoptosis
physiological function
-
caspase-8-dependent apoptosis is demonstrated by cleavage of caspase-8 after recombinant eosinophil cationic protein treatment
physiological function
-
cell death is associated with caspase-8 activation
physiological function
-
neuronal death in Tg(DELTACR) mice is not accompanied by activation of caspase-8
physiological function
-
NPI-0052 plus lenalidomide-triggered apoptosis is primarily dependent on caspase-8 signaling
physiological function
-
programmed cell death involves the caspase-8-dependent extrinsic pathway
physiological function
-
the Fas-associated protein with a death domain and subsequent activated caspase-8 are responsible for double-stranded RNA-dependent protein kinase-induced apoptosis in recombinant virus-infected cells
physiological function
-
caspase 8 can initiate apoptosis in response to cell surface receptor activation, but it is also required for embryonic development and immune cell proliferation, defined by suppression of receptor-interacting protein kinase 3, a kinase that triggers an alternative form of cell death called programmed necrosis. The extrinsic apoptosis, is mediated by a group of receptors of the tumour necrosis factor, TNF, superfamily called the death receptors. Caspase 8 is further implicated in cell motility, metastasis, and suppression of inflammation. The non-apoptotic roles of FADD and caspase 8 are involved the suppression of RIPK3-dependent programmed necrosis, the caspase 8FLIP heterodimer is implicated in carrying out the suppression of RIPK3 signalling. Mechanism of caspase 8 activation, detailed overview
physiological function
-
caspase 8 inhibits programmed necrosis by processing CYLD. Suppression of necrotic cell death by caspase 8 requires its catalytic activity but not the autocleavage essential for apoptosis. CYLD is cleaved by caspase 8 to promote survival
physiological function
-
caspase 8 inhibits programmed necrosis by processing CYLD. Suppression of necrotic cell death by caspase 8 requires its catalytic activity but not the autocleavage essential for apoptosis. CYLD is cleaved by caspase 8 to promote survival. TNF-treated caspase-8-sufficient Jurkat T cells dying by apoptosis but remain unchanged in the caspase-8-deficient cells dying by necrosis
physiological function
-
caspase 8 is an initiator caspase for caspase 3 during H2O2-induced apoptosis
physiological function
-
caspase-8 activity has an essential role in CD95/Fas-mediated MAPK activation. Stimulation of CD95/Fas/APO-1 results in the induction of both apoptotic and non-apoptotic signaling pathways. CD95 DISC-induced caspase-8 activity is important for the initiation of ERK1/2 and p38 MAPK activation, caspase-8 activation mechanism, overview. The long c-FLIP isoform, c-FLIPL, and the short c-FLIP isoform, c-FLIPR, inhibit MAPK induction by blocking caspase-8 processing at the DISC. Caspase-8 activity is also essential to MAPK activation in response to anti-APO-1 stimulation
physiological function
-
caspase-8 and caspase-7 sequentially mediate proteolytic activation of acid sphingomyelinase in TNF-R1 receptosomes. TNF-induced A-SMase activation strictly depends on functional caspase-8 and caspase-7 expression
physiological function
-
caspase-8 cleavage of the interleukin-21, IL-21, receptor is a negative feedback regulation of IL-21 signaling. Caspase-3 and the BH3 interacting domain death agonist, Bid, are cleaved by CASP8 as part of the apoptotic pathway
physiological function
-
caspase-8, the initiator of extrinsically-triggered apoptosis, also has important functions in cellular activation and differentiation downstream of a variety of cell surface receptors. The heterodimer of caspase-8 with the long isoform of cellular FLIP, FLIPL, fulfills these pro-survival functions of caspase-8. Caspase-8 has important functions in survival and development, caspase-8 activation not only triggers apoptosis but is also essential for embryonic development. Tissue specific knockout of caspase-8 revealed an essential role for this caspase in the development of a variety of tissues,most notably the endothelial cells of the heart and vascular system, lymphocytes and monocytes. Caspase-8 in programmed necrosis, detailed overview
physiological function
-
caspase-8, the initiator of extrinsically-triggered apoptosis, also has important functions in cellular activation and differentiation downstream of a variety of cell surface receptors. The heterodimer of caspase-8 with the long isoform of cellular FLIP, FLIPL, fulfills these pro-survival functions of caspase-8. Caspase-8 has important functions in survival and development. Caspase-8 in programmed necrosis, detailed overview
physiological function
-
DISC-activated caspase-8 and -10 trigger a caspase cascade by cleavage of caspase-3. Caspase-8 and Bid are the known procurers of the death signal leading from death receptor stimulation to permeabilisation of the outer mitochondrial membrane in the apoptotic pathway, regulation of caspase-8 and Bid function and activation, overview. In type II cells activation of the mitochondrial arm of the apoptosis pathway is required for the induction of apoptosis following a death receptor stimulus. The bridging element between the two arms of the apoptosis pathway is the caspase-8-mediated cleavage of the pro-apoptotic Bcl-2 family member Bid. The anionic mitochondria-specific phospho-lipid cardiolipin acts as a mitochondria-associated platform that is actually required for caspase-8 translocation, oligomerisation and activation after CD95 stimulation, and hence CD95-induced death in type II cells. In type I cells caspase-8 activation at the DISC is very efficient, resulting in direct activation of caspase-3 and the caspase cascade
physiological function
-
FADD-dependent formation of heterodimers between caspase-8 and FLIPL mediates the developmental role of caspase-8. The catalytic domain of caspase-8 is crucial for its activity in the context of activation by homodimerization. Mechanism of caspase-8 functional divergence in apoptotic and non-apoptotic pathways, overview
physiological function
-
mature caspase-8 cleaves a huge number of different cellular substrates in the cytosol. Under apoptotic stimuli, caspase-8 undergoes catalytic autocleavage to generate the proapoptotic mature tetramer to induce apoptosis
physiological function
Tumor necrosis factorrelated apoptosis-inducing ligand, TRAIL, induces degradation of cellular inhibitor of apoptosis 1, cIAP-1, requiring caspase 8 activity, for, at least in part, direct cleavage of cIAP-1 by caspase 8. Cellular depletion of cIAP-1 enhances the efficiency of TRAIL-mediated apoptosis. cIAP-1 and cIAP-2 are responsible for Lys-63 polyubiquitination of RIP1 in cancer cells, which, in turn, results in activation of NF-kappaBmediated survival signals
physiological function
caspase-8 acts as a molecular rheostat to limit RIPK1- and MyD88-mediated dendritic cell activation
physiological function
cleavage of Atg3 protein by caspase-8 regulates autophagy during receptor-activated cell death
physiological function
-
targeting of caspase-8 substrates to the plasma membrane accelerates apoptosis
physiological function
the enzyme is a key mediator of neuronal apoptosis
physiological function
caspase-10 negatively regulates caspase-8-mediated cell death. Caspase-10 reduces death-inducing signaling complex DISC association and activation of caspase-8. Caspase-10 does not compete with caspase-8 for binding to adaptor protein FADD. Caspase-8 is required upstream of both regulator cFLIP and caspase-10 and DISC formation critically depends on the scaffold function of caspase-8. Caspase-10 rewires DISC signaling to NF-kappaB activation/cell survival and the catalytic activity of caspase-10, and caspase-8, is redundant in gene induction
physiological function
-
caspase-8 of fish may play an essential role in ammonia induced apoptosis. Caspase-8 transcripts are detected in liver after exposure to ammonia. Caspase-8 cleaved fragment is detected and significant alteration of procaspase-8 level is found with the same ammonia treatment condition. Remarkable changes of immunopositive staining are observed after ammonia treatment
physiological function
cleavage by caspase 8 and the subsequent association with the outer mitochondrial membrane are two critical events that activate BH3-only protein Bid during death receptor-mediated apoptosis
physiological function
infection by Trypanosoma cruzi induces caspase-8 activity and caspase-8 inhibition increases trophoblast cells infection while decreases parasite-induced cellular differentiation and apoptotic cell death, but not cellular proliferation
physiological function
interleukin-1beta production after hypoxia might be associated with caspase-8 rather than caspase-1
additional information
-
active caspase-8 colocalizes with internalized TNF-R1 receptosomes
additional information
-
FLIPL, a catalytically defective caspase-8 paralog, can interact with caspase-8 to activate its catalytic function. The caspase-8/FLIPL heterodimer has a restricted substrate repertoire and does not induce apoptosis. Caspase-8 heterodimerized with FLIPL prevents the receptor interacting kinases RIPK1 and -3 from executing the form of cell death known as necroptosis
additional information
-
FLIPL, a catalytically defective caspase-8 paralog, can interact with caspase-8 to activate its catalytic function. The caspase-8/FLIPL heterodimer has a restricted substrate repertoire and does not induce apoptosis. Caspase-8 heterodimerized with FLIPL prevents the receptor interacting kinases RIPK1 and -3 from executing the form of cell death known as necroptosis
additional information
-
following caspase-8 recruitment to the DISC, the E3 ligase cullin-3 is able to ubiquitinate caspase-8 which in turn recruits the ubiquitin-binding protein p62, caspase-8 polyubiquitination by cullin-3 and its subsequent p62-dependent aggregation stabilises active caspase-8 and thereby positively regulates apoptosis. The caspase-8/cullin-3/p62 complex is translocates to the cytosol from where it induces apoptosis in a p62-dependent manner
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