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Information on EC 3.4.22.61 - caspase-8 and Organism(s) Homo sapiens and UniProt Accession Q14790

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EC Tree
     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.22 Cysteine endopeptidases
                3.4.22.61 caspase-8
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Select one or more organisms in this record: ?
This record set is specific for:
Homo sapiens
UNIPROT: Q14790 not found.
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
strict requirement for Asp at position P1 and has a preferred cleavage sequence of (Leu/Asp/Val)-Glu-Thr-Asp-/-(Gly/Ser/Ala)
Synonyms
caspase-8, caspase 8, casp8, flice, cysteine protease caspase-8, cysteine aspartic acid-specific protease, apoptotic cysteine protease, flice/mach, fadd-like ice, cysteine aspartic acid protease 8, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
apoptotic cysteine protease
-
-
-
-
apoptotic protease Mch-5
-
-
-
-
C14.004
-
-
-
-
CAP4
-
-
-
-
caspase 8
cysteine aspartic acid protease 8
-
-
cysteine aspartic acid-specific protease
-
-
cysteine protease caspase-8
-
-
FADD-homologous ICE/CED-3-like protease
-
-
-
-
FADD-like ICE
-
-
-
-
FLICE
FLICE/MACH
-
-
-
-
ICE-like apoptotic protease 5
-
-
-
-
MACH
-
-
-
-
Mch5
-
-
-
-
MORT1-associated CED-3 homolog
-
-
-
-
additional information
-
the enzyme belongs to the family of cysteine proteases known as caspases
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
179241-78-2
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
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
-
-
?
acetyl-DEVD-4-nitroanilide + H2O
acetyl-DEVD + 4-nitroaniline
show the reaction diagram
-
-
-
?
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
-
-
-
?
acetyl-Ile-Glu-Thr-Asp-7-amino-4-fluoromethylcoumarin + H2O
Ac-IETD + 7-amino-4-fluoromethylcoumarin
show the reaction diagram
37°C, pH 7.4
-
-
?
Atg3 protein + H2O
?
show the reaction diagram
-
-
-
?
BAP31 + H2O
?
show the reaction diagram
cleavage results in a proapoptotic p20 fragment
-
-
?
Bcl-2 protein Bid + H2O
?
show the reaction diagram
cleavage results in a proapoptotic p15 tBid fragment
-
-
?
BH3-only protein Bid + H2O
?
show the reaction diagram
-
-
-
?
Ca2+/calmodulin-dependent protein kinase-like kinase + H2O
?
show the reaction diagram
cleavage generates a 43 kDa C-terminal fragment and a small N-terminal fragment with proapoptotic activity
-
-
?
cellular inhibitor of apoptosis 1 + H2O
?
show the reaction diagram
FLICE2 + H2O
?
show the reaction diagram
-
-
-
?
HER-2 + H2O
?
show the reaction diagram
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
LAP3 + H2O
?
show the reaction diagram
-
-
-
?
LAP6 + H2O
?
show the reaction diagram
-
-
-
?
p21-activated kinase 2 + H2O
?
show the reaction diagram
separates the N-terminal regulatory domain from the C-terminal catalytic domain
-
-
?
procaspase-3 + H2O
?
show the reaction diagram
results in a p11 and p20 fragment
-
-
?
receptor-indicating protein + H2O
?
show the reaction diagram
separates the N-terminal kinase from the C-terminal death domain
-
-
?
Tx + H2O
?
show the reaction diagram
-
-
-
?
Yama + H2O
?
show the reaction diagram
-
-
-
?
Ac-IETD-4-methylcoumarin 7-amide + H2O
Ac-IETD + 7-amino-4-methylcoumarin
show the reaction diagram
-
an artificial caspase-8 substrate
-
-
?
acetyl-DEVD-7-amido-4-methylcoumarin + H2O
acetyl-DEVD + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
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
-
-
-
-
?
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
-
-
-
-
?
alpha-fodrin + H2O
?
show the reaction diagram
-
-
-
-
?
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
-
-
-
-
?
Bid protein + H2O
cleaved Bid protein
show the reaction diagram
-
i.e. BH3 interacting domain death agonist protein
-
-
?
carbonic anhydrase XIV + H2O
?
show the reaction diagram
-
cleaved at Asp53
-
-
?
caspase-3 + H2O
?
show the reaction diagram
-
-
-
-
?
CYLD + H2O
CYLDp25 + ?
show the reaction diagram
evolutionarily related interleukin-1beta converting enzyme + H2O
?
show the reaction diagram
-
ERICE i.e. evolutionarily related interleukin-1beta converting enzyme, cleavage at LEED289-/-, processing leads to the generation of two subunits
-
-
?
FLIPL protein + H2O
?
show the reaction diagram
glutaredoxin-1 + H2O
?
show the reaction diagram
-
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
-
?
HER-2 + H2O
?
show the reaction diagram
-
-
-
-
?
IEPD-7-amido-4-methylcoumarin + H2O
IEPD + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
IETD-4-nitroanilide + H2O
IETD + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
Ile-Glu-Thr-Asp-4-nitroanilide + H2O
Ile-Glu-Thr-Asp + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
interleukin-21 + 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
-
-
-
-
?
parkin + H2O
?
show the reaction diagram
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
procaspase-3 + H2O
?
show the reaction diagram
procaspase-3 + H2O
caspase-3 + ?
show the reaction diagram
procaspase-6 + H2O
caspase-6 + ?
show the reaction diagram
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
vezatin + H2O
?
show the reaction diagram
-
cleaved at Asp655
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
Atg3 protein + H2O
?
show the reaction diagram
-
-
-
?
BH3-only protein Bid + H2O
?
show the reaction diagram
-
-
-
?
cellular inhibitor of apoptosis 1 + H2O
?
show the reaction diagram
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
-
-
?
alpha-fodrin + 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
-
-
?
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
-
i.e. BH3 interacting domain death agonist protein
-
-
?
caspase-3 + H2O
?
show the reaction diagram
-
-
-
-
?
CYLD + H2O
CYLDp25 + ?
show the reaction diagram
-
key substrate processed by caspase 8 to block necrosis, CYLD is a key requirement for necrosis
-
-
?
FLIPL protein + H2O
?
show the reaction diagram
HER-2 + H2O
?
show the reaction diagram
-
-
-
-
?
interleukin-21 + H2O
?
show the reaction diagram
-
-
the CASP8-cleaved form of IL21R does not induce phosphorylation at Tyr705 of STAT3
-
?
parkin + H2O
?
show the reaction diagram
-
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
-
-
?
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
-
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
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
?
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
acetyl-IETD-aldehyde
IC50: 50 nM, covalently modifies the active site C360
benzyloxycarbonyl-DEVD-aldehyde
the inhibitor interacts favourably with the enzyme in subsite S4
benzyloxycarbonyl-IETD-fluoromethyl ketone
-
benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone
-
biotin-conjugated valine-alanine-aspartate-fluoromethylketone
-
cowpox serpin CrmA
CrmA, a pox virus-encoded serpin attenuates the ability of FLICE to activate downstrean caspases
-
Fas-associated death domain-like interleukin 1-converting enzyme-inhibitory proteins
FLIPs, natural inhibitor
-
N-acetyl-IETD-aldehyde
-
N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone
-
Q-VD-OPH
pan-caspase inhibitor
tert-butyloxycarbonyl-IETD-aldehyde
-
Z-IETD
Z-IETD-fluoromethylketone
caspase 8 inhibitor
Z-VAD
pan-caspase inhibitor
(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
-
-
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
-
-
Ac-IETD-CHO
-
-
acetyl-AEVD-aldehyde
-
-
acetyl-DEVD-aldehyde
-
-
acetyl-IETD-aldehyde
-
-
acetyl-WEHD-aldehyde
-
-
acetyl-YVAD-aldehyde
-
-
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-VAD-fluoromethylketone
benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone
-
t1/2 at 0.001 mM: 2.5 s
carboxyfluorescein-labeled-LETD-fluoromethylketone
-
-
cellular FLICE inhibitory protein
-
-
-
cFLIP
-
cowpox serpin CrmA
-
CrmA
-
inhibits caspase 8, while mutant CrmAD303A is unable to prevent cleavage of CYLD
-
FAM-LETD-FMK
-
-
FLIPL protein
-
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-carbobenzyloxy-IETD-fluoromethyl ketone
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
-
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-EVD-chloromethylketone
-
-
Z-IETD-fluoromethylketone
Z-VAD-fluoromethylketone
-
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
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
Fas-associated death domain protein-like interleukin-1-beta-converting enzyme-like inhibitory protein, long form
FLIP L, results in a heterodimeric enzyme
-
interferon-alpha
increases caspase-8 transcription
-
justicidin A
-
radiation
increases caspase-8 expression and activity
-
Sodium citrate
enhances activity
Tumor necrosis factor alpha
-
-
actinomycin D
-
significantly activates caspase-8
CD95
-
FLICE is the first in a cascade of ICE-like proteases activated by CD95. This activation requires a functional CD95 disc
-
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
-
FLIPL protein
-
a catalytically defective caspase-8 paralogue, can interact with caspase-8 to activate its catalytic function
-
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
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
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
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.066
acetyl-IETD-4-nitroanilide
pH 7.5, 37°C
0.0206 - 0.0552
acetyl-IETD-7-amido-4-fluoromethylcoumarin
0.0045
Ac-IETD-4-methylcoumarin 7-amide
-
pH 7.2, 25°C
0.004 - 0.007
acetyl-DEVD-7-amido-4-methylcoumarin
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
acetyl-IETD-7-amido-4-fluoromethylcoumarin
0.37
acetyl-DEVD-7-amido-4-methylcoumarin
-
pH 7.0 or pH 7.5
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000002
benzyloxycarbonyl-DEVD-aldehyde
-
0.000001
tert-butyloxycarbonyl-IETD-aldehyde
-
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
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
0.00005
acetyl-IETD-aldehyde
Homo sapiens
IC50: 50 nM, covalently modifies the active site C360
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
0.00045
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
25
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
no change in activity after irradiation
Manually annotated by BRENDA team
trophoblast cell line
Manually annotated by BRENDA team
the levels of caspase-3 and caspase-8 in plasma are both significantly higher than in sperm
Manually annotated by BRENDA team
OCUM-2M, OCUM-1, OCUM-8, OCUM-9, NUGC3, NIGC4, MKN45, MKN74, FU97, MKN7
Manually annotated by BRENDA team
MCF7 A/Z breast adenocarcinoma cell defective for nuclear factor kappa-B activation
Manually annotated by BRENDA team
caspase-8L is generated by the alternative splicing of human caspase-8
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
-
healthy and Parkinson disease brains, caspase-8 is selectively activated in brain tissue from patients with LRRK2 Parkinson disease
Manually annotated by BRENDA team
-
recombinant enzyme
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
-
caspase-8 is the most important factor that controls interferon and 5-fluorouracil-induced apoptosis in hepatoma cell lines
Manually annotated by BRENDA team
-
express low levels of caspase-8
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
-
caspase-8 interacts with the p85 subunit of phosphatidylinositol 3-kinase to regulate cell adhesion and motility
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
additional information
-
constitutive pro-caspase-8 protein expression
Manually annotated by BRENDA team
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
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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
evolution
malfunction
metabolism
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
CASP8_HUMAN
479
0
55391
Swiss-Prot
other Location (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
11000
alpha2beta2, 2 * 18000 + 2 * 11000, crystallographic data
18000
28000
activated heterodimer, gel filtration
31000
monomer, non-cleavable caspase-8, SDS-PAGE
43000
fragment of caspase-8 resulting from cleavage, SDS-PAGE
54000
monomer, pro-caspase-8, SDS-PAGE
55000
monomer, pro-caspase-8, SDS-PAGE
57000
monomer, full-length unactivated form, SDS-PAGE
18000
41000
-
x * 41000 + x * 43000, cleaved caspase-8, SDS-PAGE
43000
55000
-
pro-caspase-8, SDS-PAGE
57000
-
procaspase-8 shows two bands at 57000 and 43000 Da, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
monomer
tetramer
alpha2beta2, 2 * 18000 + 2 * 11000, crystallographic data
?
-
x * 41000 + x * 43000, cleaved caspase-8, SDS-PAGE
dimer
monomer
tetramer
-
dimer of dimers, 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. Under apoptotic stimuli, caspase-8 undergoes catalytic autocleavage to generate the proapoptotic mature tetramer to induce apoptosis
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
derived from a single chain proenzyme
phosphoprotein
proteolytic modification
side-chain modification
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structure of a complex of the activated caspase-8 proteolytic domain with the irreversible peptidic inhibitor benzyloxycarbonyl-EVD-dichloromethylketone, vapour diffusion method
crystallization of the enzyme covalently modified with acetyl-IETD-aldehyde, hanging- and sitting-drop vapor diffusion
structure of caspase-8 tandem death effector domains (DEDs), reveals domain-swapped dimerization. DEDs exist as dimers in solution. The FL motif on DED2 is critical for caspase-8 dimerization via domain swapping
structure of the N-terminal tandem death effector domains, DEDs and comparison with caspase 8 of Molluscum contagiosum virus subtype 1
caspase-8 in complex with beta-strand urazole ring-containing irreversible peptidomimetic inhibitor compounds 4 and 9, vapour diffusion, at 4°C, mixing of 0.002 ml inhibitor solution, containing 100 mM inhibitor, with 0.1 ml protein solution containing 8.4 mg/ml caspase-8, 20 mM Tris, 100 mM DTT, pH 8.0, incubation for 60 min, mixing of 0.0025 ml of protein complex solution with 0.0025 ml of reservoir solution containing 1.0-1.1 M citrate, 0.1 M HEPES or PIPES, pH 6.5, 4°C, X-ray diffraction structure determination and analysis at 1.8 A resolution, molecular replacement
-
crystallization of caspase-8 in complex with p35 protein from baculovirus, at 20°C by hanging-drop vapour diffusion
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D210A/D216A
cannot be cleaved to release death effector domains, overexpression inhibits the endothelial cell leukocyte adhesion molecule 1 promoter activation induced by Fas-associated death domain and receptor-interacting protein 1
E396A
diminishes TRAF6 binding capacity
E417A
diminishes TRAF6 binding capacity
F122A/I128D
mutations in the N-terminal tandem death effector domains. Mutations markedly reduce the aggregation and improve the solubility
C360S
-
a caspase-8 inactive mutant, shows no LRRK2-induced neuronal death, knockdown of caspase-8 by siRNA blocks LRRK2-induced neurotoxicity and neurodegeneration
additional information
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
caspase-8 polyubiquitination by the E3 ligase cullin-3 and its subsequent p62-dependent aggregation stabilises active caspase-8 |
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
to near homogeneity
upon refolding and purification, mature caspase-8 yields the sequences S18PRE-VETD181 and L192SSP-FPSD286, for subunits A and B, respectively, the purified enzyme shows 85% of maximum activity
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in COS-7 cells
expression in Escherichia coli
expression in HEK293T cells
CASP8, expression analysis in melanoma cells
-
determination of hypermethylation of CASP8 promoter in stem-cell-like glioma cells, whereas non-stem-cell-like glioma cells exhibit a non-methylated CASP8 promoter, expression analysis, overview
-
expressed in HeLa cells
-
expressed in Neuro-2A and HeLa cells
-
expression analysis of caspase-8 in absence and presence of poly(ADP-ribose) polymerase 1, PARP-1, expression, the caspase-8 expression is not influenced
-
expression analysis of caspase-8 in B-cell chronic lymphocytic leukemia compared to healthy B-cells, overview
-
gene CASP8, expression analysis, analysis of promoter methylation status, hypermethylation of the CASP8 promoter in stem-cell-like glioma cells
-
gene CASP8, located at chromosome 2q33-q34, DNA and amino acid sequence determination and analysis, quantitative expression analysis in neuroblastoma cells by RT-PCR, determination of methylation status of a CpG island located between exons 2 and 3 of caspase 8 in neuroblastomas, methylation inactivates the geneoverview
-
proMch5 lacking the two N-terminal FADD-like domains are subcloned in the bacterial expression vector pET21b in frame with an N-terminal T7 tag and a C-terminal His6tag. Bacterial expression generates a mature enzyme composed of two subunits, which are derived from the precursor by processing at Asp227, Asp233, Asp391 and Asp401
-
transient coexpression of caspase wild-type parkin in HEK-293 cells identifies caspase-1, caspase-3 and caspase-8 as efficient inducers of parkin cleavage
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
tumor necrosis factor–related apoptosis-inducing ligand, TRAIL, signaling induces caspase 8
30 h after treatment with ionizing radiation (20 Gy), there is an activation of caspase 8
-
4 mM butyrate and propionate but not acetate can induce non-activated and lipopolysaccharide- or tumor necrosis factor-alpha-activated neutrophil apoptosis by caspase-8 pathway
-
a significant downregulation in CASP8 expression is observed after cell activation in multiple sclerosis patients homozygotes for the protective (ACT/ACT) and risk haplotypes (GCA/GCA)
-
after cecropin A treatment for 24 h at concentrations of 0.03 or 0.04 mM, the activity of caspase-8 does not increase
-
caspase-8 activity remains low when human gingival epithelial cells are incubated with 50 ng/ml H2S in air containing 5% CO2 for 24, 48 or 72 h
-
caspase-8 is activated by arsenic trioxide during neutrophil apoptosis, after 3 h a slight caspase-8 activity is observed only in arsenic trioxide-induced neutrophils
-
Dryopteris crassirhizoma extract (0.1 mg/ml for 24-48 h) causes the cleavage of pro-caspase-8 in PC3-MM2 cells, indicating the increased activity of this caspase
-
eosinophil cationic protein induces caspase-8 activation through mitochondria-independent pathway
-
expression, nuclear fragmentation and caspase-8 activation are not decreased significantly in R393E mutant C-terminal pseudo death effector domain of HIPPI-cells in comparison to that obtained with wild type C-terminal pseudo death effector domain of HIPPI-cells
-
extracellular signal-regulated kinase activity induces caspase-8 activation
-
genistein triggers the receptor-mediated apoptotic pathway through activation of caspase-8, the highest activation of caspase-8 occurs after treatment with the combination of Bcl-2 siRNA and genistein (0.01 mM)
-
histone deacetylase inhibition leads to transcriptional suppression of cellular FLIP, which negatively regulates extrinsic apoptosis by preventing the recruitment of caspase-8 to the death-inducing signaling complex
-
in cells exposed to 0.5 mM UDP for 4.5 h, the activation of caspase-8 increases about 3fold
-
inactivation of protein-associated splicing factor by siRNA significantly decreases the level of caspase-8 in macrophages, significant suppression of caspase-8 activation is observed in both macrophages infected with wild type Mycobacterium tuberculosis H37Rv and with the complemented 31G12 strain containing the pLD31G12-3 construct
-
no change in caspase-8 expressions is observed in ischemic preconditioning livers
-
NPI-0052 plus lenalidomide-induced apoptosis is associated with activation of caspase-8
-
procaspase-8 is cleaved after evodiamine treatment (0.001 and 0.01 mM) for 36 h and increases significantly at 60 h
-
processing of caspase-8 and its enzymatic activity is reduced in Chlamydia trachomatis-infected cells and coincides with a decrease in Bid truncation, caspase-8 inhibition by Chlamydia is dependent on cFlip
-
recombinant tumor necrosis actor-alpha-treated and Mycobacterium tuberculosis 31G12-infected macrophages show caspase-8 activation
-
simvastatin does not induce caspase-8 activity
-
sperm samples of Robertsonian translocation carrier patients show a higher proportion of spermatozoa with activated caspase-8 than those from fertile donors
-
staurosporine-induced apoptosis induces caspase-8 activation
-
the majority (78.3%) of HeLa cells reveals an activated caspase-8 after 8 h of coculture with adipose-derived-mesenchymal stromal/stem cell tumor necrosis factor-related apoptosis-inducing ligand
-
there is an increase in active caspase-8 within 4 h of Helicobacter pylori infection in APE-1-downregulated cells relative to the control cells
-
there is no significant increase of caspase-8 activity in 0.05 mM goniothalamin treatment from 2 up to 12 h
-
transient expression of GFP-Hippi in cells with reduced Huntingtin interacting protein-1 significantly decreases nuclear fragmentation and caspase-8 activation
-
treatment with 0.05 mM (2R,3S)-3',4',5,7-tetrahydroxyflavan-3-yl decanoate (catechin-C10) increases caspase-8 activity after 4 and 6 h
-
[Me(2)Ga(S-imi)](2) causes apoptosis by upregulation of caspases 8
-
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
upon refolding and purification, mature caspase-8 yields the sequences S18PRE-VETD181 and L192SSP-FPSD286, for subunits A and B, respectively, the purified enzyme shows 85% of maximum activity
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
gastric cancer might be a good target of TRAIL therapy because the majority of tumor cells have intact caspase-8 expression. The anticancer efficacy may be predicted by the degree of caspase-8 activation after TRAIL treatment
medicine
drug development
-
caspase-8 ia a target for structure-based drug design approach
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Garcia-Calvo, M.; Peterson, E.P.; Leiting, B.; Ruel, R.; Nicholson, D.W.; Thornberry, N.A.
Inhibition of human caspases by peptide-based and macromolecular inhibitors
J. Biol. Chem.
273
32608-32613
1998
Homo sapiens
Manually annotated by BRENDA team
Garcia-Calvo, M.; Peterson, E.P.; Rasper, D.M.; Vaillancourt, J.P.; Zamboni, R.; Nicholson, D.W.; Thornberry, N.A.
Purification and catalytic properties of human caspase family members
Cell Death Differ.
6
362-369
1999
Homo sapiens
Manually annotated by BRENDA team
Chang, H.Y.; Yang, X.
Proteases from cell suicide: functions and regulation of caspases
Microbiol. Mol. Biol. Rev.
64
821-846
2000
Homo sapiens
Manually annotated by BRENDA team
Thornberry, N.A.; Rano, T.A.; Peterson, E.P.; et al.
A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis
J. Biol. Chem.
272
17907-17911
1997
Homo sapiens
Manually annotated by BRENDA team
Boldin, M.P.; Goncharov, T.M.; Goltsev, Y.V.; Wallach, D.
Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death
Cell
85
803-815
1996
Homo sapiens (Q14790)
Manually annotated by BRENDA team
Fernandes-Alnemri, T.; Armstrong, R.C.; Krebs, J.F.; Srinivasula, S.M.; Wang, L.; Bullrich, F.; Fritz, L.C.; Trapani, J.A.; Tomaselli, K.J.; Litwack, G.; Alnemri, E.S.
In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains
Proc. Natl. Acad. Sci. USA
93
7464-7469
1996
Homo sapiens (Q14790), Homo sapiens
Manually annotated by BRENDA team
Himeji, D.; Horiuchi, T.; Tsukamoto, H.; Hayashi, K.; Watanabe, T.; Harada, M.
Characterization of caspase-8L: a novel isoform of caspase-8 that behaves as an inhibitor of the caspase cascade
Blood
99
4070-4078
2002
Homo sapiens (Q14790), Homo sapiens
Manually annotated by BRENDA team
Muzio, M.; Salvesen, G.S.; Dixit, V.M.
FLICE induced apoptosis in a cell-free system. Cleavage of caspase zymogens
J. Biol. Chem.
272
2952-2956
1997
Homo sapiens (Q14790)
Manually annotated by BRENDA team
Ng, F.W.H.; Nguyen, M.; Kwan, T.; Branton, P.E.; Nicholson, D.W.; Cromlish, J.A.; Shore, G.C.
p28 Bap31, a Bcl-2/Bcl-XL- and procaspase-8-associated protein in the endoplasmic reticulum
J. Cell Biol.
139
327-338
1997
Homo sapiens (Q14790), Homo sapiens
Manually annotated by BRENDA team
Blanchard, H.; Kodandapani, L.; Mittl, P.R.E.; Di Marco, S.; Krebs, J.F.; Wu, J.C.; Tomaselli, K.J.; Gruetter, M.G.
The three-dimensional structure of caspase-8: an initiator enzyme in apoptosis
Structure
7
1125-1133
1999
Homo sapiens (Q14790), Homo sapiens
Manually annotated by BRENDA team
Blanchard, H.; Donepudi, M.; Tschopp, M.; Kodandapani, L.; Wu, J.C.; Grutter, M.G.
Caspase-8 specificity probed at subsite S(4): crystal structure of the caspase-8-Z-DEVD-CHO complex
J. Mol. Biol.
302
9-16
2000
Homo sapiens (Q14790)
Manually annotated by BRENDA team
Humke, E.W.; Ni, J.; Dixit, V.M.
ERICE, a novel FLICE-activatable caspase
J. Biol. Chem.
273
15702-15707
1998
Homo sapiens
Manually annotated by BRENDA team
Li, H.; Zhu, H.; Xu, C.J.; Yuan, J.
Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis
Cell
94
491-501
1998
Homo sapiens
Manually annotated by BRENDA team
Watt, W.; Koeplinger, K.A.; Mildner, A.M.; Heinrikson, R.L.; Tomasselli, A.G.; Watenpaugh, K.D.
The atomic-resolution structure of human caspase-8, a key activator of apoptosis
Structure Fold. Des.
7
1135-1143
1999
Homo sapiens (Q14790), Homo sapiens
Manually annotated by BRENDA team
Xu, G.; Cirilli, M.; Huang, Y.; Rich, R.L.; Myszka, D.G.; Wu, H.
Covalent inhibition revealed by the crystal structure of the caspase-8/p35 complex
Nature
410
494-497
2001
Homo sapiens
Manually annotated by BRENDA team
Muzio, M.; Chinnaiyan, A.M.; Kischkel, F.C.; O`Rourke, K.; et al.
FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex
Cell
85
817-827
1996
Homo sapiens
Manually annotated by BRENDA team
Medema, J.P.; Scaffidi, C.; Kischkel, F.C.; Shevchenko, A.; Mann, M.; Krammer, P.H.; Peter, M.E.
FLICE is activated by association with the CD95 death-inducing signaling complex (DISC)
EMBO J.
16
2794-2804
1997
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Srinivasula, S.M.; Ahmad, M.; Fernandes-Almeri, T.; Liwack, G.; Alnemri, E.S.
Molecular ordering of the Fas-apoptotic pathway: the fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteien proteases
Proc. Natl. Acad. Sci. USA
93
14486-14491
1996
Homo sapiens
Manually annotated by BRENDA team
Chang, D.W.; Xing, Z.; Capacio, V.L.; Peter, M.E.; Yang, X.
Inerdimer processing mechanism of procaspase-8 activation
EMBO J.
22
4132-4142
2003
Homo sapiens
Manually annotated by BRENDA team
Kahns, S.; Kalai, M.; Jakobsen, L.D.; Clark, B.F.; Vandenabeele, P.; Jensen, P.H.
Caspase-1 and caspase-8 cleave and inactivate cellular parkin
J. Biol. Chem.
278
23376-23380
2003
Homo sapiens
Manually annotated by BRENDA team
Breckenridge, D.G.; Nguyen, M.; Kuppig, S.; Reth, M.; Shore, G.C.
The procaspase-8 isoform, procaspase-8L, recruited to the BAP31 complex at the endoplasmic reticulum
Proc. Natl. Acad. Sci. USA
99
4331-4336
2002
Homo sapiens (Q14790)
Manually annotated by BRENDA team
Chun, H.J.; Zheng, L.; Ahman, M.; Wang, J.; Speirs, C.K.; Siegel, R.M.; Dale, J.K.; Puck, J.; Davis, J.; Hall, C.G.; Skoda-Smith, S.; Atkinson, T.P.; Straus, S.E.; Lenardo, M.J.
Pleiotrophic defects in lamphocyte activation caused by caspase-8 mutations lead to human immunodeficiency
Nature
419
395-399
2002
Homo sapiens
Manually annotated by BRENDA team
Juo, P.; Kuo, C.J.; Yuan, J.; Blenis, J.
Essential requiremnt for caspase-8/FLICE in the initiation of the Fas-induced apoptotic cascade
Curr. Biol.
8
1001-1008
1998
Homo sapiens
Manually annotated by BRENDA team
Stennicke, H.R.; Jrgensmeier, J.M.; Shin, H.; et.al.
Pro-caspase-3 is major physiologic target of caspase-8
J. Biol. Chem.
273
27084-27099
1998
Homo sapiens
Manually annotated by BRENDA team
Boatright, K.M.; Deis, C.; Denault, J.B.; Sutherlin, D.P.; Salvesen, G.S.
Activiation of caspases-8 and -10 by FLIP L
Biochem. J.
382
651-657
2004
Homo sapiens (Q14790)
Manually annotated by BRENDA team
Benoit, V.; Chariot, A.; Delacroix, L.; Deregowski, V.; Jacobs, N.; Merville, M.P.; Bours, V.
Caspase-8-dependent HER-2 cleavage in response to tumor necrosis factor alpha stimulation is counteracted by nuclear factor kappaB through c-FLIP-L expression
Cancer Res.
64
2684-2691
2004
Homo sapiens (Q14790), Homo sapiens
Manually annotated by BRENDA team
Afshar, G.; Jelluma, N.; Yang, X.; Basila, D.; Arvold, N.D.; Karlsson, A.; Yount, G.L.; Dansen, T.B.; Koller, E.; Haas-Kogan, D.A.
Radiation-induced caspase-8 mediates p53-independent apoptosis in glioma cells
Cancer Res.
66
4223-4232
2006
Homo sapiens (Q14790)
Manually annotated by BRENDA team
Bidere, N.; Snow, A.L.; Sakai, K.; Zheng, L.; Lenardo, M.J.
Caspase-8 Regulation by Direct Interaction with TRAF6 in T Cell Receptor-Induced NF-kappaB Activation
Curr. Biol.
16
1666-1671
2006
Homo sapiens (Q14790)
Manually annotated by BRENDA team
Su, C.L.; Huang, L.L.; Huang, L.M.; Lee, J.C.; Lin, C.N.; Won, S.J.
Caspase-8 acts as a key upstream executor of mitochondria during justicidin A-induced apoptosis in human hepatoma cells
FEBS Lett.
580
3185-3191
2006
Homo sapiens (Q14790), Homo sapiens
Manually annotated by BRENDA team
Jenkins, C.E.; Swiatoniowski, A.; Issekutz, A.C.; Lin, T.J.
Pseudomonas aeruginosa exotoxin A induces human mast cell apoptosis by a caspase-8 and -3-dependent mechanism
J. Biol. Chem.
279
37201-37207
2004
Homo sapiens (Q14790), Homo sapiens
Manually annotated by BRENDA team
Liedtke, C.; Groeger, N.; Manns, M.P.; Trautwein, C.
Interferon-alpha enhances TRAIL-mediated apoptosis by up-regulating caspase-8 transcription in human hepatoma cells
J. Hepatol.
44
342-349
2006
Homo sapiens (Q14790), Homo sapiens
Manually annotated by BRENDA team
Takahashi, K.; Kawai, T.; Kumar, H.; Sato, S.; Yonehara, S.; Akira, S.
Roles of caspase-8 and caspase-10 in innate immune responses to double-stranded RNA
J. Immunol.
176
4520-4524
2006
Homo sapiens (Q14790), Homo sapiens
Manually annotated by BRENDA team
Fischer, U.; Stroh, C.; Schulze-Osthoff, K.
Unique and overlapping substrate specificities of caspase-8 and caspase-10
Oncogene
25
152-159
2006
Homo sapiens (Q14790)
Manually annotated by BRENDA team
Kanehara, I.; Nakata, B.; Hirakawa, K.
Caspase-8 is scarcely silenced and its activity is well correlated with the anticancer effect of tumor necrosis factor-related apoptosis-inducing ligand in gastric cancer cells
Oncol. Rep.
14
1249-1253
2005
Homo sapiens (Q14790)
Manually annotated by BRENDA team
Senft, J.; Helfer, B.; Frisch, S.M.
Caspase-8 interacts with the p85 subunit of phosphatidylinositol 3-kinase to regulate cell adhesion and motility
Cancer Res.
67
11505-11509
2007
Homo sapiens
Manually annotated by BRENDA team
Qi, W.; Wu, H.; Yang, L.; Boyd, D.D.; Wang, Z.
A novel function of caspase-8 in the regulation of androgen-receptor-driven gene expression
EMBO J.
26
65-75
2007
Homo sapiens
Manually annotated by BRENDA team
Koike, K.; Takaki, A.; Tatsukawa, M.; Suzuki, M.; Shiraha, H.; Iwasaki, Y.; Sakaguchi, K.; Shiratori, Y.
Combination of 5-FU and IFNalpha enhances IFN signaling pathway and caspase-8 activity, resulting in marked apoptosis in hepatoma cell lines
Int. J. Oncol.
29
1253-1261
2006
Homo sapiens
Manually annotated by BRENDA team
Barbero, S.; Barila, D.; Mielgo, A.; Stagni, V.; Clair, K.; Stupack, D.
Identification of a critical tyrosine residue in caspase 8 that promotes cell migration
J. Biol. Chem.
283
13031-13034
2008
Homo sapiens
Manually annotated by BRENDA team
Calvaruso, G.; Giuliano, M.; Portanova, P.; De Blasio, A.; Vento, R.; Tesoriere, G.
Bortezomib induces in HepG2 cells IkappaBalpha degradation mediated by caspase-8
Mol. Cell. Biochem.
287
13-19
2006
Homo sapiens
Manually annotated by BRENDA team
Byun, H.S.; Song, J.K.; Kim, Y.R.; Piao, L.; Won, M.; Park, K.A.; Choi, B.L.; Lee, H.; Hong, J.H.; Park, J.; Seok, J.H.; Lee, Y.J.; Kang, S.W.; Hur, G.M.
Caspase-8 has an essential role in resveratrol-induced apoptosis of rheumatoid fibroblast-like synoviocytes
Rheumatology
47
301-308
2008
Homo sapiens
Manually annotated by BRENDA team
Capper, D.; Gaiser, T.; Hartmann, C.; Habel, A.; Mueller, W.; Herold-Mende, C.; von Deimling, A.; Siegelin, M.D.
Stem-cell-like glioma cells are resistant to TRAIL/Apo2L and exhibit down-regulation of caspase-8 by promoter methylation
Acta Neuropathol.
117
445-456
2009
Homo sapiens
Manually annotated by BRENDA team
Abe, A.; Yamada, H.
Harmol induces apoptosis by caspase-8 activation independently on Fas/Fas ligand interaction in human lung carcinoma H596 cells
Anticancer Drugs
20
373-381
2009
Homo sapiens
Manually annotated by BRENDA team
Cheah, Y.H.; Nordin, F.J.; Tee, T.T.; Azimahtol, H.L.; Abdullah, N.R.; Ismail, Z.
Antiproliferative property and apoptotic effect of xanthorrhizol on MDA-MB-231 breast cancer cells
Anticancer Res.
28
3677-3689
2009
Homo sapiens
Manually annotated by BRENDA team
Ideo, A.; Hashimoto, K.; Shimada, J.; Kawase, M.; Sakagami, H.
Type of cell death induced by alpha-trifluoromethyl acyloins in oral squamous cell carcinoma
Anticancer Res.
29
175-181
2009
Homo sapiens
Manually annotated by BRENDA team
Artwohl, M.; Lindenmair, A.; Roden, M.; Waldhaeusl, W.K.; Freudenthaler, A.; Klosner, G.; Ilhan, A.; Luger, A.; Baumgartner-Parzer, S.M.
Fatty acids induce apoptosis in human smooth muscle cells depending on chain length, saturation, and duration of exposure
Atherosclerosis
202
351-362
2009
Homo sapiens
Manually annotated by BRENDA team
Beurel, E.; Blivet-Van Eggelpoel, M.J.; Kornprobst, M.; Moritz, S.; Delelo, R.; Paye, F.; Housset, C.; Desbois-Mouthon, C.
Glycogen synthase kinase-3 inhibitors augment TRAIL-induced apoptotic death in human hepatoma cells
Biochem. Pharmacol.
77
54-65
2009
Homo sapiens
Manually annotated by BRENDA team
Balsas, P.; Lopez-Royuela, N.; Galan-Malo, P.; Anel, A.; Marzo, I.; Naval, J.
Cooperation between Apo2L/TRAIL and bortezomib in multiple myeloma apoptosis
Biochem. Pharmacol.
77
804-812
2009
Homo sapiens
Manually annotated by BRENDA team
Chen, X.Y.; Yang, H.X.; Qu, S.F.; Liu, J.; Lv, P.; Xu, J.P.; Xu, K.S.
Involvement of p38 and c-Jun N-terminal protein kinase in cardiotoxin III-induced apoptosis of K562 cells
Biol. Pharm. Bull.
32
583-588
2009
Homo sapiens
Manually annotated by BRENDA team
Carlucci, F.; Marinello, E.; Tommassini, V.; Pisano, B.; Rosi, F.; Tabucchi, A.
A 57-gene expression signature in B-cell chronic lymphocytic leukemia
Biomed. Pharmacother.
63
663-671
2009
Homo sapiens
Manually annotated by BRENDA team
Bonofiglio, D.; Gabriele, S.; Aquila, S.; Qi, H.; Belmonte, M.; Catalano, S.; Ando, S.
Peroxisome proliferator-activated receptor gamma activates fas ligand gene promoter inducing apoptosis in human breast cancer cells
Breast Cancer Res. Treat.
113
423-434
2009
Homo sapiens
Manually annotated by BRENDA team
Fuchs, O.; Provaznikova, D.; Marinov, I.; Kuzelova, K.; Spicka, I.
Antiproliferative and proapoptotic effects of proteasome inhibitors and their combination with histone deacetylase inhibitors on leukemia cells
Cardiovasc. Hematol. Disord. Drug Targets
9
62-77
2009
Homo sapiens
Manually annotated by BRENDA team
Inoue, S.; Browne, G.; Melino, G.; Cohen, G.M.
Ordering of caspases in cells undergoing apoptosis by the intrinsic pathway
Cell Death Differ.
16
1053-1061
2009
Homo sapiens
Manually annotated by BRENDA team
Choi, E.J.; Ahn, W.S.; Bae, S.M.
Equol induces apoptosis through cytochrome c-mediated caspases cascade in human breast cancer MDA-MB-453 cells
Chem. Biol. Interact.
177
7-11
2009
Homo sapiens
Manually annotated by BRENDA team
Goel, A.; Prasad, A.K.; Parmar, V.S.; Ghosh, B.; Saini, N.
Apoptogenic effect of 7,8-diacetoxy-4-methylcoumarin and 7,8-diacetoxy-4-methylthiocoumarin in human lung adenocarcinoma cell line: role of NF-kappaB, Akt, ROS and MAP kinase pathway
Chem. Biol. Interact.
179
363-374
2009
Homo sapiens
Manually annotated by BRENDA team
Huang, S.; Okumura, K.; Sinicrope, F.A.
BH3 mimetic obatoclax enhances TRAIL-mediated apoptosis in human pancreatic cancer cells
Clin. Cancer Res.
15
150-159
2009
Homo sapiens
Manually annotated by BRENDA team
Chen, Y.X.; Lv, W.G.; Chen, H.Z.; Ye, F.; Xie, X.
Methotrexate induces apoptosis of human choriocarcinoma cell line JAR via a mitochondrial pathway
Eur. J. Obstet. Gynecol. Reprod. Biol.
143
107-111
2009
Homo sapiens
Manually annotated by BRENDA team
Chen, N.; Gong, J.; Chen, X.; Meng, W.; Huang, Y.; Zhao, F.; Wang, L.; Zhou, Q.
Caspases and inhibitor of apoptosis proteins in cutaneous and mucosal melanoma: expression profile and clinicopathologic significance
Hum. Pathol.
40
950-956
2009
Homo sapiens
Manually annotated by BRENDA team
Jin, D.; Ojcius, D.M.; Sun, D.; Dong, H.; Luo, Y.; Mao, Y.; Yan, J.
Leptospira interrogans induces apoptosis in macrophages via caspase-8- and caspase-3-dependent pathways
Infect. Immun.
77
799-809
2009
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Albrecht, E.A.; Sarma, J.V.; Ward, P.A.
Activation by C5a of endothelial cell caspase 8 and cFLIP
Inflamm. Res.
58
30-37
2009
Homo sapiens
Manually annotated by BRENDA team
Hu, G.; Barnes, B.J.
IRF-5 is a mediator of the death receptor-induced apoptotic signaling pathway
J. Biol. Chem.
284
2767-2777
2009
Homo sapiens
Manually annotated by BRENDA team
Kadohara, K.; Nagumo, M.; Asami, S.; Tsukumo, Y.; Sugimoto, H.; Igarashi, M.; Nagai, K.; Kataoka, T.
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
J. Biol. Chem.
284
5478-5487
2009
Homo sapiens
Manually annotated by BRENDA team
Anathy, V.; Aesif, S.W.; Guala, A.S.; Havermans, M.; Reynaert, N.L.; Ho, Y.S.; Budd, R.C.; Janssen-Heininger, Y.M.
Redox amplification of apoptosis by caspase-dependent cleavage of glutaredoxin 1 and S-glutathionylation of Fas
J. Cell Biol.
184
241-252
2009
Homo sapiens
Manually annotated by BRENDA team
Alam, M.M.; Mohammad, A.A.; Shuaib, U.; Wang, C.; Ghani, U.; Schwindt, B.; Todd, K.G.; Shuaib, A.
Homocysteine reduces endothelial progenitor cells in stroke patients through apoptosis
J. Cereb. Blood Flow Metab.
29
157-165
2009
Homo sapiens
Manually annotated by BRENDA team
Delloye-Bourgeois, C.; Brambilla, E.; Coissieux, M.M.; Guenebeaud, C.; Pedeux, R.; Firlej, V.; Cabon, F.; Brambilla, C.; Mehlen, P.; Bernet, A.
Interference with netrin-1 and tumor cell death in non-small cell lung cancer
J. Natl. Cancer Inst.
101
237-247
2009
Homo sapiens
Manually annotated by BRENDA team
Ho, C.C.; Rideout, H.J.; Ribe, E.; Troy, C.M.; Dauer, W.T.
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
J. Neurosci.
29
1011-1016
2009
Homo sapiens
Manually annotated by BRENDA team
Heo, S.K.; Yun, H.J.; Park, W.H.; Park, S.D.
Rhein inhibits TNF-alpha-induced human aortic smooth muscle cell proliferation via mitochondrial-dependent apoptosis
J. Vasc. Res.
46
375-386
2009
Homo sapiens
Manually annotated by BRENDA team
Gupta, S.; Agrawal, S.; Gollapudi, S.
Differential effect of human herpesvirus 6A on cell division and apoptosis among naive and central and effector memory CD4+ and CD8+ T-cell subsets
J. Virol.
83
5442-5450
2009
Homo sapiens
Manually annotated by BRENDA team
Chen, Y.W.; Lin, G.J.; Chia, W.T.; Lin, C.K.; Chuang, Y.P.; Sytwu, H.K.
Triptolide exerts anti-tumor effect on oral cancer and KB cells in vitro and in vivo
Oral Oncol.
45
562-568
2009
Homo sapiens
Manually annotated by BRENDA team
Kamimatsuse, A.; Matsuura, K.; Moriya, S.; Fukuba, I.; Yamaoka, H.; Fukuda, E.; Kamei, N.; Hiyama, K.; Sueda, T.; Hiyama, E.
Detection of CpG island hypermethylation of caspase-8 in neuroblastoma using an oligonucleotide array
Pediatr. Blood Cancer
52
777-783
2009
Homo sapiens
Manually annotated by BRENDA team
Gajate, C.; Gonzalez-Camacho, F.; Mollinedo, F.
Involvement of raft aggregates enriched in Fas/CD95 death-inducing signaling complex in the antileukemic action of edelfosine in Jurkat cells
PLoS ONE
4
e5044
2009
Homo sapiens
Manually annotated by BRENDA team
Garcia, S.; Mera, A.; Gomez-Reino, J.J.; Conde, C.
Poly(ADP-ribose) polymerase suppression protects rheumatoid synovial fibroblasts from Fas-induced apoptosis
Rheumatology
48
483-489
2009
Homo sapiens
Manually annotated by BRENDA team
Chattopadhyay, R.; Bhattacharyya, A.; Crowe, S.E.
Dual regulation by apurinic/apyrimidinic endonuclease-1 inhibits gastric epithelial cell apoptosis during Helicobacter pylori infection
Cancer Res.
70
2799-2808
2010
Homo sapiens
Manually annotated by BRENDA team
Chaopatchayakul, P.; Jearanaikoon, P.; Yuenyao, P.; Limpaiboon, T.
Aberrant DNA methylation of apoptotic signaling genes in patients responsive and nonresponsive to therapy for cervical carcinoma
Am. J. Obstet. Gynecol.
202
281e1-281e9
2010
Homo sapiens
Manually annotated by BRENDA team
Esposti, D.D.; Domart, M.C.; Sebagh, M.; Harper, F.; Pierron, G.; Brenner, C.; Lemoine, A.
Autophagy is induced by ischemic preconditioning in human livers formerly treated by chemotherapy to limit necrosis
Autophagy
6
172-174
2010
Homo sapiens
Manually annotated by BRENDA team
Ghavami, S.; Mutawe, M.M.; Hauff, K.; Stelmack, G.L.; Schaafsma, D.; Sharma, P.; McNeill, K.D.; Hynes, T.S.; Kung, S.K.; Unruh, H.; Klonisch, T.; Hatch, G.M.; Los, M.; Halayko, A.J.
Statin-triggered cell death in primary human lung mesenchymal cells involves p53-PUMA and release of Smac and Omi but not cytochrome c
Biochim. Biophys. Acta
1803
452-467
2010
Homo sapiens
Manually annotated by BRENDA team
Chauhan, D.; Singh, A.V.; Ciccarelli, B.; Richardson, P.G.; Palladino, M.A.; Anderson, K.C.
Combination of novel proteasome inhibitor NPI-0052 and lenalidomide trigger in vitro and in vivo synergistic cytotoxicity in multiple myeloma
Blood
115
834-845
2010
Homo sapiens
Manually annotated by BRENDA team
Chang, K.C.; Lo, C.W.; Fan, T.C.; Chang, M.D.; Shu, C.W.; Chang, C.H.; Chung, C.T.; Fang, S.L.; Chao, C.C.; Tsai, J.J.; Lai, Y.K.
TNF-alpha mediates eosinophil cationic protein-induced apoptosis in BEAS-2B cells
BMC Cell Biol.
11
6-6
2010
Homo sapiens
Manually annotated by BRENDA team
Grisendi, G.; Bussolari, R.; Cafarelli, L.; Petak, I.; Rasini, V.; Veronesi, E.; De Santis, G.; Spano, C.; Tagliazzucchi, M.; Barti-Juhasz, H.; Scarabelli, L.; Bambi, F.; Frassoldati, A.; Rossi, G.; Casali, C.; Morandi, U.; Horwitz, E.M.; Paolucci, P.; Conte, P.; Dominici, M.
Adipose-derived mesenchymal stem cells as stable source of tumor necrosis factor-related apoptosis-inducing ligand delivery for cancer therapy
Cancer Res.
70
3718-3729
2010
Homo sapiens
Manually annotated by BRENDA team
Boehme, L.; Albrecht, M.; Riede, O.; Rudel, T.
Chlamydia trachomatis-infected host cells resist dsRNA-induced apoptosis
Cell. Microbiol.
12
1340-1351
2010
Homo sapiens
Manually annotated by BRENDA team
Ahmed, K.; Wei, Z.L.; Zhao, Q.L.; Nakajima, N.; Matsunaga, T.; Ogasawara, M.; Kondo, T.
Role of fatty acid chain length on the induction of apoptosis by newly synthesized catechin derivatives
Chem. Biol. Interact.
185
182-188
2010
Homo sapiens
Manually annotated by BRENDA team
Bidle, K.A.; Haramaty, L.; Baggett, N.; Nannen, J.; Bidle, K.D.
Tantalizing evidence for caspase-like protein expression and activity in the cellular stress response of Archaea
Environ. Microbiol.
12
1161-1172
2010
Homo sapiens (Q14790), Homo sapiens
Manually annotated by BRENDA team
Cagnol, S.; Chambard, J.C.
ERK and cell death: mechanisms of ERK-induced cell death--apoptosis, autophagy and senescence
FEBS J.
277
2-21
2010
Homo sapiens
Manually annotated by BRENDA team
Brugnon, F.; Janny, L.; Communal, Y.; Darcha, C.; Szczepaniak, C.; Pellestor, F.; Vago, P.; Pons-Rejraji, H.; Artonne, C.; Grizard, G.
Apoptosis and meiotic segregation in ejaculated sperm from Robertsonian translocation carrier patients
Hum. Reprod.
25
1631-1642
2010
Homo sapiens
Manually annotated by BRENDA team
Binet, F.; Chiasson, S.; Girard, D.
Arsenic trioxide induces endoplasmic reticulum stress-related events in neutrophils
Int. Immunopharmacol.
10
508-512
2010
Homo sapiens
Manually annotated by BRENDA team
Darvas, K.; Rosenberger, S.; Brenner, D.; Fritsch, C.; Gmelin, N.; Krammer, P.H.; Roesl, F.
Histone deacetylase inhibitor-induced sensitization to TNFalpha/TRAIL-mediated apoptosis in cervical carcinoma cells is dependent on HPV oncogene expression
Int. J. Cancer
127
1384-1392
2010
Homo sapiens
Manually annotated by BRENDA team
Gallego, B.; Kaluderovic, M.R.; Kommera, H.; Paschke, R.; Hey-Hawkins, E.; Remmerbach, T.W.; Kaluderovic, G.N.; Gomez-Ruiz, S.
Cytotoxicity, apoptosis and study of the DNA-binding properties of bi- and tetranuclear gallium(III) complexes with heterocyclic thiolato ligands
Invest. New Drugs
29
932-944
2011
Homo sapiens
Manually annotated by BRENDA team
Bleicken, S.; Classen, M.; Padmavathi, P.V.; Ishikawa, T.; Zeth, K.; Steinhoff, H.J.; Bordignon, E.
Molecular details of Bax activation, oligomerization, and membrane insertion
J. Biol. Chem.
285
6636-6647
2010
Homo sapiens
Manually annotated by BRENDA team
Chen, M.C.; Yu, C.H.; Wang, S.W.; Pu, H.F.; Kan, S.F.; Lin, L.C.; Chi, C.W.; Ho, L.L.; Lee, C.H.; Wang, P.S.
Anti-proliferative effects of evodiamine on human thyroid cancer cell line ARO
J. Cell. Biochem.
110
1495-1503
2010
Homo sapiens
Manually annotated by BRENDA team
Chang, S.H.; Bae, J.H.; Hong, D.P.; Choi, K.D.; Kim, S.C.; Her, E.; Kim, S.H.; Kang, C.D.
Dryopteris crassirhizoma has anti-cancer effects through both extrinsic and intrinsic apoptotic pathways and G0/G1 phase arrest in human prostate cancer cells
J. Ethnopharmacol.
130
248-254
2010
Homo sapiens
Manually annotated by BRENDA team
Bai, X.; Kim, S.H.; Azam, T.; McGibney, M.T.; Huang, H.; Dinarello, C.A.; Chan, E.D.
IL-32 is a host protective cytokine against Mycobacterium tuberculosis in differentiated THP-1 human macrophages
J. Immunol.
184
3830-3840
2010
Homo sapiens
Manually annotated by BRENDA team
Camina-Tato, M.; Fernandez, M.; Morcillo-Suarez, C.; Navarro, A.; Julia, E.; Edo, M.C.; Montalban, X.; Comabella, M.
Genetic association of CASP8 polymorphisms with primary progressive multiple sclerosis
J. Neuroimmunol.
222
70-75
2010
Homo sapiens
Manually annotated by BRENDA team
Chae, S.S.; Yoo, C.B.; Jo, C.; Yun, S.M.; Jo, S.A.; Koh, Y.H.
Caspases-2 and -8 are involved in the presenilin1/gamma-secretase-dependent cleavage of amyloid precursor protein after the induction of apoptosis
J. Neurosci. Res.
88
1926-1933
2010
Homo sapiens
Manually annotated by BRENDA team
George, J.; Banik, N.L.; Ray, S.K.
Genistein induces receptor and mitochondrial pathways and increases apoptosis during BCL-2 knockdown in human malignant neuroblastoma SK-N-DZ cells
J. Neurosci. Res.
88
877-886
2010
Homo sapiens
Manually annotated by BRENDA team
Calenic, B.; Yaegaki, K.; Murata, T.; Imai, T.; Aoyama, I.; Sato, T.; Ii, H.
Oral malodorous compound triggers mitochondrial-dependent apoptosis and causes genomic DNA damage in human gingival epithelial cells
J. Periodontal Res.
45
31-37
2010
Homo sapiens
Manually annotated by BRENDA team
Aguzzi, M.S.; Fortugno, P.; Giampietri, C.; Ragone, G.; Capogrossi, M.C.; Facchiano, A.
Intracellular targets of RGDS peptide in melanoma cells
Mol. Cancer
9
84
2010
Homo sapiens
Manually annotated by BRENDA team
Bijangi-Vishehsaraei, K.; Saadatzadeh, M.R.; Huang, S.; Murphy, M.P.; Safa, A.R.
4-(4-Chloro-2-methylphenoxy)-N-hydroxybutanamide (CMH) targets mRNA of the c-FLIP variants and induces apoptosis in MCF-7 human breast cancer cells
Mol. Cell. Biochem.
342
133-142
2010
Homo sapiens
Manually annotated by BRENDA team
Apolloni, S.; Finocchi, P.; DAgnano, I.; Alloisio, S.; Nobile, M.; DAmbrosi, N.; Volonte, C.
UDP exerts cytostatic and cytotoxic actions in human neuroblastoma SH-SY5Y cells over-expressing P2Y6 receptor
Neurochem. Int.
56
670-678
2010
Homo sapiens
Manually annotated by BRENDA team
Banerjee, M.; Datta, M.; Majumder, P.; Mukhopadhyay, D.; Bhattacharyya, N.P.
Transcription regulation of caspase-1 by R393 of HIPPI and its molecular partner HIP-1
Nucleic Acids Res.
38
878-892
2010
Homo sapiens
Manually annotated by BRENDA team
Aoyama, M.; Kotani, J.; Usami, M.
Butyrate and propionate induced activated or non-activated neutrophil apoptosis via HDAC inhibitor activity but without activating GPR-41/GPR-43 pathways
Nutrition
26
653-661
2010
Homo sapiens
Manually annotated by BRENDA team
Giotakis, J.; Gomatos, I.P.; Alevizos, L.; Georgiou, A.N.; Leandros, E.; Konstadoulakis, M.M.; Manolopoulos, L.
Bax, cytochrome c, and caspase-8 staining in parotid cancer patients: markers of susceptibility in radiotherapy?
Otolaryngol. Head Neck Surg.
142
605-611
2010
Homo sapiens
Manually annotated by BRENDA team
Cho, S.; Lee, J.H.; Cho, S.B.; Yoon, K.W.; Park, S.Y.; Lee, W.S.; Park, C.H.; Joo, Y.E.; Kim, H.S.; Choi, S.K.; Rew, J.S.
Epigenetic methylation and expression of caspase 8 and survivin in hepatocellular carcinoma
Pathol. Int.
60
203-211
2010
Homo sapiens
Manually annotated by BRENDA team
Ceron, J.M.; Contreras-Moreno, J.; Puertollano, E.; Cienfuegos, G.A.; Puertollano, M.A.; de Pablo, M.A.
The antimicrobial peptide cecropin A induces caspase-independent cell death in human promyelocytic leukemia cells
Peptides
31
1494-1503
2010
Homo sapiens
Manually annotated by BRENDA team
Gauster, M.; Huppertz, B.
The paradox of caspase 8 in human villous trophoblast fusion
Placenta
31
82-88
2010
Homo sapiens
Manually annotated by BRENDA team
Danelishvili, L.; Yamazaki, Y.; Selker, J.; Bermudez, L.E.
Secreted Mycobacterium tuberculosis Rv3654c and Rv3655c proteins participate in the suppression of macrophage apoptosis
PLoS ONE
5
e10474
2010
Homo sapiens
Manually annotated by BRENDA team
Chan, K.M.; Rajab, N.F.; Siegel, D.; Din, L.B.; Ross, D.; Inayat-Hussain, S.H.
Goniothalamin induces coronary artery smooth muscle cells apoptosis: the p53-dependent caspase-2 activation pathway
Toxicol. Sci.
116
533-548
2010
Homo sapiens
Manually annotated by BRENDA team
Bertollo, C.M.; Correa, C.R.; Gomes, D.A.; Souza-Fagundes, E.M.; Goes, A.M.
Effect of radiation treatment on newly established human breast cancer cell lines MACL-1 and MGSO-3
Tumour Biol.
31
189-197
2010
Homo sapiens
Manually annotated by BRENDA team
Wang, Z.; Watt, W.; Brooks, N.A.; Harris, M.S.; Urban, J.; Boatman, D.; McMillan, M.; Kahn, M.; Heinrikson, R.L.; Finzel, B.C.; Wittwer, A.J.; Blinn, J.; Kamtekar, S.; Tomasselli, A.G.
Kinetic and structural characterization of caspase-3 and caspase-8 inhibition by a novel class of irreversible inhibitors
Biochim. Biophys. Acta
1804
1817-1831
2010
Homo sapiens
Manually annotated by BRENDA team
Kantari, C.; Walczak, H.
Caspase-8 and Bid: caught in the act between death receptors and mitochondria
Biochim. Biophys. Acta
1813
558-563
2011
Homo sapiens
Manually annotated by BRENDA team
van Raam, B.J.; Salvesen, G.S.
Proliferative versus apoptotic functions of caspase-8 hetero or homo: the caspase-8 dimer controls cell fate
Biochim. Biophys. Acta
1824
113-122
2012
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Kober, A.M.; Legewie, S.; Pforr, C.; Fricker, N.; Eils, R.; Krammer, P.H.; Lavrik, I.N.
Caspase-8 activity has an essential role in CD95/Fas-mediated MAPK activation
Cell Death Dis.
2
e212
2011
Homo sapiens
Manually annotated by BRENDA team
Wu, Y.; Wang, D.; Wang, X.; Wang, Y.; Ren, F.; Chang, D.; Chang, Z.; Jia, B.
Caspase 3 is activated through caspase 8 instead of caspase 9 during H2O2-induced apoptosis in HeLa cells
Cell. Physiol. Biochem.
27
539-546
2011
Homo sapiens
Manually annotated by BRENDA team
Edelmann, B.; Bertsch, U.; Tchikov, V.; Winoto-Morbach, S.; Perrotta, C.; Jakob, M.; Adam-Klages, S.; Kabelitz, D.; Schuetze, S.
Caspase-8 and caspase-7 sequentially mediate proteolytic activation of acid sphingomyelinase in TNF-R1 receptosomes
EMBO J.
30
379-394
2011
Homo sapiens
Manually annotated by BRENDA team
Guicciardi, M.E.; Mott, J.L.; Bronk, S.F.; Kurita, S.; Fingas, C.D.; Gores, G.J.
Cellular inhibitor of apoptosis 1 (cIAP-1) degradation by caspase 8 during TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis
Exp. Cell Res.
317
107-116
2011
Homo sapiens (Q14790), Homo sapiens
Manually annotated by BRENDA team
Akagi, T.; Shimizu, K.; Takahama, S.; Iwasaki, T.; Sakamaki, K.; Endo, Y.; Sawasaki, T.
Caspase-8 cleavage of the interleukin-21 (IL-21) receptor is a negative feedback regulator of IL-21 signaling
FEBS Lett.
585
1835-1840
2011
Homo sapiens
Manually annotated by BRENDA team
Zhao, Y.; Sui, X.; Ren, H.
From procaspase-8 to caspase-8: revisiting structural functions of caspase-8
J. Cell. Physiol.
225
316-320
2010
Homo sapiens
Manually annotated by BRENDA team
O'Donnell, M.A.; Perez-Jimenez, E.; Oberst, A.; Ng, A.; Massoumi, R.; Xavier, R.; Green, D.R.; Ting, A.T.
Caspase 8 inhibits programmed necrosis by processing CYLD
Nat. Cell Biol.
13
1437-1442
2011
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Oberst, A.; Green, D.R.
It cuts both ways: reconciling the dual roles of caspase 8 in cell death and survival
Nat. Rev. Mol. Cell Biol.
12
757-763
2011
Homo sapiens
Manually annotated by BRENDA team
Oral, O.; Oz-Arslan, D.; Itah, Z.; Naghavi, A.; Deveci, R.; Karacali, S.; Gozuacik, D.
Cleavage of Atg3 protein by caspase-8 regulates autophagy during receptor-activated cell death
Apoptosis
17
810-820
2012
Homo sapiens (Q14790)
Manually annotated by BRENDA team
Ahmad, K.; Khan, S.; Adil, M.; Saeed, M.; Srivastava, A.K.
Structure based molecular inhibition of Caspase-8 for treatment of multi-neurodegenerative diseases using known natural compounds
Bioinformation
10
191-195
2014
Homo sapiens (Q14790)
Manually annotated by BRENDA team
Beaudouin, J.; Liesche, C.; Aschenbrenner, S.; Hoerner, M.; Eils, R.
Caspase-8 cleaves its substrates from the plasma membrane upon CD95-induced apoptosis
Cell Death Differ.
20
599-610
2013
Homo sapiens
Manually annotated by BRENDA team
Li, X.; Zhao, Y.; Zhang, Y.; Du, N.; Ren, H.
Tumor necrosis factor alpha stimulates Her-2 cleavage by activated caspase-8
Cell. Physiol. Biochem.
30
889-897
2012
Homo sapiens
Manually annotated by BRENDA team
Shen, C.; Yue, H.; Pei, J.; Guo, X.; Wang, T.; Quan, J.M.
Crystal structure of the death effector domains of caspase-8
Biochem. Biophys. Res. Commun.
463
297-302
2015
Homo sapiens (Q14790)
Manually annotated by BRENDA team
Park, H.H.
Molecular basis of dimerization of initiator caspase was revealed by crystal structure of caspase-8 pro-domain
Cell Death Differ.
26
1213-1220
2019
Homo sapiens (Q14790)
Manually annotated by BRENDA team
Horn, S.; Hughes, M.A.; Schilling, R.; Sticht, C.; Tenev, T.; Ploesser, M.; Meier, P.; Sprick, M.R.; MacFarlane, M.; Leverkus, M.
Caspase-10 negatively regulates caspase-8-mediated cell death, switching the response to CD95L in favor of NF-kappaB activation and cell survival
Cell Rep.
19
785-797
2017
Homo sapiens (Q14790)
Manually annotated by BRENDA team
Saavedra, E.; Del Rosario, H.; Brouard, I.; Quintana, J.; Estevez, F.
6-Benzyloxy-4-bromo-2-hydroxychalcone is cytotoxic against human leukaemia cells and induces caspase-8- and reactive oxygen species-dependent apoptosis
Chem. Biol. Interact.
298
137-145
2019
Homo sapiens (Q14790)
Manually annotated by BRENDA team
Carrillo, I.; Droguett, D.; Castillo, C.; Liempi, A.; Munoz, L.; Maya, J.D.; Galanti, N.; Kemmerling, U.
Caspase-8 activity is part of the BeWo trophoblast cell defense mechanisms against Trypanosoma cruzi infection
Exp. Parasitol.
168
9-15
2016
Homo sapiens (Q14790)
Manually annotated by BRENDA team
Wei, X.; Li, Q.; Han, Z.; Lin, D.; Yu, P.
Differences in caspase-8 and -9 activity and sperm motility in infertile males of Li nationality in China
Int. J. Clin. Exp. Med.
8
4721-4726
2015
Homo sapiens (Q14790), Homo sapiens
Manually annotated by BRENDA team
Huang, K.; Zhang, J.; ONeill, K.L.; Gurumurthy, C.B.; Quadros, R.M.; Tu, Y.; Luo, X.
Cleavage by caspase 8 and mitochondrial membrane association activate the BH3-only protein Bid during TRAIL-induced apoptosis
J. Biol. Chem.
291
11843-11851
2016
Homo sapiens (Q14790)
Manually annotated by BRENDA team