Information on EC 3.4.22.61 - caspase-8

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
3.4.22.61
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RECOMMENDED NAME
GeneOntology No.
caspase-8
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
strict requirement for Asp at position P1 and has a preferred cleavage sequence of (Leu/Asp/Val)-Glu-Thr-Asp-/-(Gly/Ser/Ala)
show the reaction diagram
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
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additional information
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caspase-8 also regulates cell motility
CAS REGISTRY NUMBER
COMMENTARY hide
179241-78-2
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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Manually annotated by BRENDA team
strain GDH 2346
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Manually annotated by BRENDA team
strain GDH 2346
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Manually annotated by BRENDA team
strain AAHB 4479
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Manually annotated by BRENDA team
strain AAHB 4479
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
strain 129/SvJ
SwissProt
Manually annotated by BRENDA team
Balb/c mice
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Manually annotated by BRENDA team
C57BL/6 mice
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Manually annotated by BRENDA team
C57Bl6 mice
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Manually annotated by BRENDA team
strain Glasgow
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Manually annotated by BRENDA team
strain Glasgow
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(aspartyl)2-rhodamine 110 + H2O
?
show the reaction diagram
Ac-IEPD-7-amido-4-methylcoumarin + H2O
Ac-IEPD + 7-amino-4-methylcoumarin
show the reaction diagram
-
37°C
-
-
?
Ac-IEPD-AMC + H2O
Ac-IEPD + AMC
show the reaction diagram
-
37°C
-
-
?
Ac-IETD-4-methylcoumarin 7-amide + H2O
Ac-IETD + 7-amino-4-methylcoumarin
show the reaction diagram
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an artificial caspase-8 substrate
-
-
?
Ac-IETD-7-amido-4-methylcoumarin + H2O
Ac-IETD + 7-amino-4-methylcoumarin
show the reaction diagram
acetyl-DEVD-4-nitroanilide + H2O
acetyl-DEVD + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
acetyl-DEVD-7-amido-4-methylcoumarin + H2O
acetyl-DEVD + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
acetyl-DEVD-p-nitroanilide + H2O
acetyl-DEVD + p-nitroaniline
show the reaction diagram
-
49% of the activity with acetyl-IETD-p-nitroanilide
-
-
?
acetyl-IETD-4-nitroanilide + H2O
acetyl-IETD + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
acetyl-IETD-7-amido-4-fluoromethylcoumarin + H2O
acetyl-IETD + 7-amino-4-fluoromethylcoumarin
show the reaction diagram
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-
-
-
?
acetyl-IETD-p-nitroanilide + H2O
acetyl-IETD + p-nitroaniline
show the reaction diagram
-
-
-
-
?
acetyl-Ile-Glu(OMe)-Thr-Asp(OMe)-7-amido-4-trifluoromethylcoumarin + H2O
acetyl-Ile-Glu(OMe)-Thr-Asp(OMe) + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
acetyl-Ile-Glu-Thr-Asp-7-amino-4-fluoromethylcoumarin + H2O
Ac-IETD + 7-amino-4-fluoromethylcoumarin
show the reaction diagram
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37°C, pH 7.4
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-
?
acetyl-LEHD-p-nitroanilide + H2O
acetyl-LEHD + p-nitroaniline
show the reaction diagram
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142% of the activity with acetyl-IETD-p-nitroanilide
-
-
?
acetyl-VDVAD-p-nitroanilide + H2O
acetyl-VDVAD + p-nitroaniline
show the reaction diagram
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36% of the activity with acetyl-IETD-p-nitroanilide
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-
?
acetyl-VEID-p-nitroanilide + H2O
acetyl-VEID + p-nitroaniline
show the reaction diagram
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76% of the activity with acetyl-IETD-p-nitroanilide
-
-
?
acetyl-WEHD-p-nitroanilide + H2O
acetyl-WEHD + p-nitroaniline
show the reaction diagram
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64% of the activity with acetyl-IETD-p-nitroanilide
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?
alpha-fodrin + H2O
?
show the reaction diagram
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-
?
Atg3 protein + H2O
?
show the reaction diagram
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-
-
-
?
BAP31 + H2O
?
show the reaction diagram
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cleavage results in a proapoptotic p20 fragment
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?
basic transcription factor 3 + H2O
?
show the reaction diagram
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?
Bcl-2 + H2O
?
show the reaction diagram
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?
Bcl-2 protein Bid + H2O
?
show the reaction diagram
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cleavage results in a proapoptotic p15 tBid fragment
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?
benzyloxycarbonyl-IETD-7-amido-4-trifluoromethylcoumarin + H2O
benzyloxycarbonyl-IETD + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
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-
-
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?
beta-catenin + H2O
?
show the reaction diagram
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?
BID + H2O
?
show the reaction diagram
Bid + H2O
tBid + ?
show the reaction diagram
Bid peptide + H2O
?
show the reaction diagram
Bid peptide + H2O
truncated Bid peptide + ?
show the reaction diagram
Bid protein + H2O
?
show the reaction diagram
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?
Bid protein + H2O
cleaved Bid protein
show the reaction diagram
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i.e. BH3 interacting domain death agonist protein
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?
Ca2+/calmodulin-dependent protein kinase-like kinase + H2O
?
show the reaction diagram
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cleavage generates a 43 kDa C-terminal fragment and a small N-terminal fragment with proapoptotic activity
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?
carbonic anhydrase XIV + H2O
?
show the reaction diagram
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cleaved at Asp53
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?
carboxypeptidase E + H2O
?
show the reaction diagram
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?
caspase-3 + H2O
?
show the reaction diagram
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?
cellular FLIP long form + H2O
?
show the reaction diagram
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?
cellular inhibitor of apoptosis 1 + H2O
?
show the reaction diagram
CYLD + H2O
CYLDp25 + ?
show the reaction diagram
DEVD-rhodamine + H2O
rhodamine + DEVD
show the reaction diagram
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?
Dopey family membrane 1 + H2O
?
show the reaction diagram
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?
evolutionarily related interleukin-1beta converting enzyme + H2O
?
show the reaction diagram
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ERICE i.e. evolutionarily related interleukin-1beta converting enzyme, cleavage at LEED289-/-, processing leads to the generation of two subunits
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?
FLICE + H2O
?
show the reaction diagram
37°C
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?
FLICE2 + H2O
?
show the reaction diagram
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?
FLIPL + H2O
?
show the reaction diagram
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the cleavage sequence for caspase-8 is LEVD/G
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?
FLIPL protein + H2O
?
show the reaction diagram
fluorescein isothiocyanate + H2O
?
show the reaction diagram
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37°C, pH 7.4
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?
glutaredoxin-1 + H2O
?
show the reaction diagram
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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
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?
Golgi associated PDZ and coiled-coil motif containing trancription variant 1 + H2O
?
show the reaction diagram
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?
HDAC-7 + H2O
?
show the reaction diagram
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the cleavage sequence for caspase-8 is LETD/G
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?
HER-2 + H2O
?
show the reaction diagram
IEPD-7-amido-4-methylcoumarin + H2O
IEPD + 7-amino-4-methylcoumarin
show the reaction diagram
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-
-
-
?
IETD-4-nitroanilide + H2O
IETD + 4-nitroaniline
show the reaction diagram
IETD-7-amido-4-trifluoromethylcoumarin + H2O
IETD + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
Ile-Glu-Thr-Asp-4-nitroanilide + H2O
Ile-Glu-Thr-Asp + 4-nitroaniline
show the reaction diagram
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-
-
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?
interleukin-21 + H2O
?
show the reaction diagram
kinase anchor protein 1 + H2O
?
show the reaction diagram
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?
LAP3 + H2O
?
show the reaction diagram
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?
LAP6 + H2O
?
show the reaction diagram
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-
-
?
LETD-4-nitroanilide + H2O
LETD + 4-nitroaniline
show the reaction diagram
-
-
-
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?
N-acetyl-IETD-4-nitroanilide + H2O
N-acetyl-IETD + 4-nitroaniline
show the reaction diagram
N-acetyl-IETD-4-nitroanilide + H2O
N-acetyl-IETD + 4-nitroaniline + H2O
show the reaction diagram
N-acetyl-IETD-4-trifluoromethylcoumarin 7-amide + H2O
N-acetyl-IETD + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
nuclear export signal-LQTDG + H2O
?
show the reaction diagram
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-
-
-
?
p21-activated kinase 2 + H2O
?
show the reaction diagram
-
separates the N-terminal regulatory domain from the C-terminal catalytic domain
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?
parkin + H2O
?
show the reaction diagram
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
procaspase-10 + H2O
caspase-3 + ?
show the reaction diagram
-
the cleavage sequence in procaspase-10, catalytically inactive C285A mutant, for caspase-8 is IEAD/A
-
-
?
procaspase-3 + H2O
?
show the reaction diagram
procaspase-3 + H2O
active caspase-3 + ?
show the reaction diagram
procaspase-3 + H2O
caspase-3 + ?
show the reaction diagram
procaspase-6 + H2O
caspase-6 + ?
show the reaction diagram
procaspase-7 + H2O
caspase-3 + ?
show the reaction diagram
-
the cleavage sequence in procaspase-7, catalytically inactive C285A mutant, for caspase-8 is IQAD/S
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?
procaspase-8 + H2O
caspase-8 + ?
show the reaction diagram
receptor-indicating protein + H2O
?
show the reaction diagram
RIPK1 + H2O
?
show the reaction diagram
Tx + H2O
?
show the reaction diagram
-
-
-
?
vezatin + H2O
?
show the reaction diagram
-
cleaved at Asp655
-
-
?
Yama + H2O
?
show the reaction diagram
-
-
-
?
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
alpha-fodrin + H2O
?
show the reaction diagram
-
-
-
-
?
Atg3 protein + H2O
?
show the reaction diagram
-
-
-
-
?
BID + H2O
?
show the reaction diagram
-
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 + H2O
tBid + ?
show the reaction diagram
Bid peptide + H2O
?
show the reaction diagram
Bid peptide + H2O
truncated Bid peptide + ?
show the reaction diagram
Bid protein + H2O
?
show the reaction diagram
-
-
-
-
?
Bid protein + H2O
cleaved Bid protein
show the reaction diagram
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i.e. BH3 interacting domain death agonist protein
-
-
?
caspase-3 + H2O
?
show the reaction diagram
-
-
-
-
?
cellular inhibitor of apoptosis 1 + H2O
?
show the reaction diagram
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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
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?
CYLD + H2O
CYLDp25 + ?
show the reaction diagram
FLIPL protein + H2O
?
show the reaction diagram
HER-2 + H2O
?
show the reaction diagram
-
-
-
-
?
interleukin-21 + H2O
?
show the reaction diagram
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the CASP8-cleaved form of IL21R does not induce phosphorylation at Tyr705 of STAT3
-
?
parkin + H2O
?
show the reaction diagram
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cleavage at Asp126-Ser127. Caspase-1 and caspase-8 dependent parkin cleavage in sporadic Parkinson‘s 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 + ?
show the reaction diagram
-
caspase-3 is activated through caspase-8 during H2O2-induced apoptosis in HeLa cells
-
-
?
procaspase-3 + H2O
?
show the reaction diagram
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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 + ?
show the reaction diagram
-
direct activation by caspase-8 in type I cells
-
-
?
procaspase-3 + H2O
caspase-3 + ?
show the reaction diagram
procaspase-6 + H2O
caspase-6 + ?
show the reaction diagram
-
cleavage of caspases 3 and 6 by caspase-8 results in apoptosis
-
-
?
procaspase-8 + H2O
caspase-8 + ?
show the reaction diagram
-
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
?
show the reaction diagram
-
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
?
show the reaction diagram
-
cleaved at Asp655
-
-
?
additional information
?
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(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
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(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
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-
(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
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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
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-
(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
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-
(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
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-
2'-nitroflavone
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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
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Ac-IETD-CHO
acetyl-AEVD-aldehyde
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acetyl-Asp-Glu-Val-Asp-al
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acetyl-DEVD-aldehyde
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acetyl-IETD-aldehyde
acetyl-Ile-Glu-Thr-Asp-al
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acetyl-Leu-Glu-His-Asp-al
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acetyl-Val-Asp-Val-Ala-Asp-al
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0.01 mM, 80% inhibition
acetyl-WEHD-aldehyde
-
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acetyl-YVAD-aldehyde
-
-
benzyloxycarbonyl-DEVD-aldehyde
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the inhibitor interacts favourably with the enzyme in subsite S4
benzyloxycarbonyl-IETD-fluoromethyl ketone
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-
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
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-
benzyloxycarbonyl-VAD-fluoromethylketone
benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone
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-
benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone
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t1/2 at 0.001 mM: 2.5 s
benzyloxycarbonyl-Val-Asp-Val-Ala-Asp-fluoromethylketone
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benzyloxycarbonyl-valyl-alanyl-aspartic acid (O-methyl)-fluoro-methylketone
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biotin-conjugated valine-alanine-aspartate-fluoromethylketone
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c-FLIP
-
-
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carboxyfluorescein-labeled-LETD-fluoromethylketone
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-
carboxyfluorescein-LETD-fluoromethylketone
-
-
Cbz-Val-Ala-Asp[O-methyl]-fluoromethylketone
-
pan-caspase inhibitor
cellular FLICE inhibitory protein
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-
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cFLIP
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cowpox serpin CrmA
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CP-IETD-cho
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CrmA
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FAM-LETD-FMK
-
-
Fas-associated death domain-like interleukin 1-converting enzyme-inhibitory proteins
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FLIPs, natural inhibitor
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FLIPL protein
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IETD-CHO
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specific caspase-8 inhibitor
IETD-fluoromethyl ketone
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a caspase-8-specific inhibitor
IETD-fluoromethylketone
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IETD-fmk
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Ile-Glu-Thr-Asp-[O-methyl]-fluoromethylketone
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N-acetyl-IETD-aldehyde
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-
-
N-benzyloxycarbonyl-VAD-fluoromethyl ketone
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a general caspase inhibitor
N-benzyloxycarbonyl-VAD-fluoromethylketone
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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
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Q-VD-OPH
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pan-caspase inhibitor
QVD-OPh
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tert-butyloxycarbonyl-IETD-aldehyde
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triptolide
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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
viral FLIP
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-
Z-EVD-chloromethylketone
Z-IETD
Z-IETD-fluoromethyl ketone
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Z-IETD-fluoromethylketone
Z-VAD
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pan-caspase inhibitor
Z-VAD-fluoromethylketone
Z-Val-Ala-Asp(OCH3)-fluoromethylketone
-
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
actinomycin D
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significantly activates caspase-8
CD95
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cellular FLIP long form
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complement factor 5a
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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
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edelfosine
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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
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FLIPL protein
-
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
-
justicidin A
-
-
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
staurosporine
-
-
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
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0045
Ac-IETD-4-methylcoumarin 7-amide
-
pH 7.2, 25°C
0.0206 - 0.0552
Ac-IETD-fluoromethylcoumarin
0.004 - 0.007
acetyl-DEVD-7-amido-4-methylcoumarin
0.066
acetyl-IETD-4-nitroanilide
-
pH 7.5, 37°C
additional information
additional information
-
stopped-flow and steady-state kinetics
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.65 - 1.25
Ac-IETD-fluoromethylcoumarin
0.37
acetyl-DEVD-7-amido-4-methylcoumarin
Homo sapiens
-
pH 7.0 or pH 7.5
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0000016
acetyl-AEVD-aldehyde
-
pH 7.5, 25°C
0.00000092
acetyl-DEVD-aldehyde
-
pH 7.5, 25°C
0.00000105
acetyl-IETD-aldehyde
-
pH 7.5, 25°C
0.0000211
acetyl-WEHD-aldehyde
-
pH 7.5, 25°C
0.000352
acetyl-YVAD-aldehyde
-
pH 7.5, 25°C
0.000002
benzyloxycarbonyl-DEVD-aldehyde
-
-
0.000001
tert-butyloxycarbonyl-IETD-aldehyde
-
-
additional information
additional information
-
inhibition kinetics, first-order inhibition kinetics, and two-step irreversible inhibition mechanism
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00354
(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
Homo sapiens
-
pH 7.2, 25°C
0.0031
(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
Homo sapiens
-
pH 7.2, 25°C
0.00152
(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
Homo sapiens
-
pH 7.2, 25°C
0.00132
(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
Homo sapiens
-
pH 7.2, 25°C
0.00644
(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
Homo sapiens
-
pH 7.2, 25°C
0.00357
(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
Homo sapiens
-
pH 7.2, 25°C
0.00927
(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
Homo sapiens
-
pH 7.2, 25°C
0.00363
(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
Homo sapiens
-
pH 7.2, 25°C
0.00033
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
Homo sapiens
-
pH 7.2, 25°C
0.00005
acetyl-IETD-aldehyde
Homo sapiens
-
IC50: 50 nM, covalently modifies the active site C360
0.00045
N-benzyloxycarbonyl-VAD-fluoromethylketone
Homo sapiens
-
pH 7.2, 25°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 7.5
-
reaction with acetyl-DEVD-7-amido-4-methylcoumari
7.2
-
assay at
7.5
-
assay at
8
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
-
assay at room temperature
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
cleaved caspase-8 is detected in apoptotic cells in the adrenal gland
Manually annotated by BRENDA team
-
ipsilateral side
Manually annotated by BRENDA team
-
ofloxacin induces apoptosis in microencapsulated juvenile rabbit chondrocytes by caspase-8-dependent mitochondrial pathway
Manually annotated by BRENDA team
-
recombinant enzyme
Manually annotated by BRENDA team
-
OCUM-2M, OCUM-1, OCUM-8, OCUM-9, NUGC3, NIGC4, MKN45, MKN74, FU97, MKN7
Manually annotated by BRENDA team
-
NCH421K_SCG, NCH441_SCG, NCH421K_NSCG; NCH441_SCG, NCH421K_SCG, NCH421K_NSCG
Manually annotated by BRENDA team
high expression
Manually annotated by BRENDA team
-
caspase-8 is the most important factor that controls interferon and 5-fluorouracil-induced apoptosis in hepatoma cell lines
Manually annotated by BRENDA team
-
a oral squamous cell carcinoma cell line
Manually annotated by BRENDA team
-
a oral squamous cell carcinoma cell line
Manually annotated by BRENDA team
-
express low levels of caspase-8
Manually annotated by BRENDA team
-
STI571-resistant cells
Manually annotated by BRENDA team
-
casp8 is maternally expressed, and transcripts continue to be present throughout embryogenesis and into larval stages
Manually annotated by BRENDA team
highest expression
Manually annotated by BRENDA team
-
expression patterns of the major caspases, CASP3, 6, 7, 8, 9, and 10, and inhibitor of apoptosis proteins, survivin, CIAP1, CIAP2, XIAP, and livin, overview
Manually annotated by BRENDA team
-
expression patterns of the major caspases, CASP3, 6, 7, 8, 9, and 10, and inhibitor of apoptosis proteins, survivin, CIAP1, CIAP2, XIAP, and livin, overview
Manually annotated by BRENDA team
adult ventricular myocyte
Manually annotated by BRENDA team
-
caspase-8 interacts with the p85 subunit of phosphatidylinositol 3-kinase to regulate cell adhesion and motility
Manually annotated by BRENDA team
-
Casp8 is essential for beta-cell apoptosis in type 1 and type 2 diabetes models and in regulating beta-cell mass and insulin secretion under physiological conditions
Manually annotated by BRENDA team
-
caspase-8L is generated by the alternative splicing of human caspase-8
Manually annotated by BRENDA team
-
caspase-8 is the most important factor that controls interferon and 5-fluorouracil-induced apoptosis in hepatoma cell lines
Manually annotated by BRENDA team
-
activation of caspase-8 is essential for triggering resveratrol-induced apoptotic signalling via the involvement of the mitochondrial pathway in rheumatoid arthritis fibroblast-like synoviocytes. 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
Manually annotated by BRENDA team
-
caspase-8 expression is increased in the orbito-frontal cortex 14 days after spared nerve injury of the sciatic nerve, prevented by ozone
Manually annotated by BRENDA team
-
increase in caspase-8 transcript levels and activity after irradiation
Manually annotated by BRENDA team
-
increase in caspase-8 transcript levels and activity after irradiation
Manually annotated by BRENDA team
-
no change in activity after irradiation
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
in addition to its cytosolic distribution, caspase 8 is recruited to lamella of migrating cells
Manually annotated by BRENDA team
-
nuclear colocalization of caspase-8 and Fas-associated death domain, FADD
Manually annotated by BRENDA team
-
caspase-8 is significantly more active at the plasma membrane than within the cytosol upon CD95 activation
Manually annotated by BRENDA team
additional information