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Information on EC 3.4.22.61 - caspase-8 and Organism(s) Mus musculus and UniProt Accession O89110
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3.4.22.61 caspase-8Specify your search results
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- 3.4.22.61
- caspase-9
- bcl-2
- necrosis
-
extrinsic
- bid
- tnf
-
trail
-
apoptosis-inducing
- parp
-
pro-apoptotic
-
anti-apoptotic
- leukemia
-
fas-associated
-
trail-induced
-
tunel
- fasl
-
annexin
-
death-inducing
-
factor-related
-
caspase-dependent
- c-flips
-
apoptosis-related
- xiap
-
fas-mediated
- flip
-
receptor-mediated
- nf-kappab
-
polyadp-ribose
-
jurkat
-
necroptosis
-
anti-fas
-
deoxynucleotidyl
- adp-ribose
-
pan-caspase
- z-vad-fmk
-
tnf-related
-
deltapsim
-
mitochondria-dependent
-
fas-induced
- survivin
-
receptor-induced
-
tnf-induced
-
receptor-interacting
- mlkl
-
mitochondria-mediated
- ripk1
-
sub-g1
- apaf-1
-
executioner
- drug development
- procaspase-3
- medicine
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
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, cysteine aspartic acid protease 8, fadd-like ice, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
apoptotic cysteine protease
-
-
-
-
apoptotic protease Mch-5
-
-
-
-
C14.004
-
-
-
-
CAP4
-
-
-
-
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
-
-
-
-
caspase 8
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
179241-78-2
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
receptor-indicating protein + H2O
?
separates the N-terminal kinase from the C-terminal death domain
-
-
?
Ac-IETD-7-amido-4-methylcoumarin + H2O
Ac-IETD + 7-amino-4-methylcoumarin
-
-
-
-
?
acetyl-Ile-Glu(OMe)-Thr-Asp(OMe)-7-amido-4-trifluoromethylcoumarin + H2O
acetyl-Ile-Glu(OMe)-Thr-Asp(OMe) + 7-amino-4-trifluoromethylcoumarin
-
-
-
-
?
benzyloxycarbonyl-IETD-7-amido-4-trifluoromethylcoumarin + H2O
benzyloxycarbonyl-IETD + 7-amino-4-trifluoromethylcoumarin
-
-
-
-
?
Golgi associated PDZ and coiled-coil motif containing trancription variant 1 + H2O
?
-
-
-
-
?
IETD-7-amido-4-trifluoromethylcoumarin + H2O
IETD + 7-amino-4-trifluoromethylcoumarin
-
a specific caspase-8 substrate
-
-
?
N-acetyl-IETD-4-trifluoromethylcoumarin 7-amide + H2O
N-acetyl-IETD + 7-amino-4-trifluoromethylcoumarin
-
-
-
-
?
procaspase-10 + H2O
caspase-3 + ?
-
the cleavage sequence in procaspase-10, catalytically inactive C285A mutant, for caspase-8 is IEAD/A
-
-
?
procaspase-7 + H2O
caspase-3 + ?
-
the cleavage sequence in procaspase-7, catalytically inactive C285A mutant, for caspase-8 is IQAD/S
-
-
?
procaspase-8 + H2O
caspase-8 + ?
-
the autocleavage sequences of procaspase-8 monomers are VETD/S and LEMD/L, and of procaspase-8 dimers VETD/S and LEMD/L
-
-
?
CYLD + H2O
CYLDp25 + ?
-
key substrate processed by caspase 8 to block necrosis, CYLD is a key requirement for necrosis of L929 fibrosarcoma cells
-
-
?
CYLD + H2O
CYLDp25 + ?
-
caspase 8 directly cleaves CYLD after Asp 215, an Asp215 CYLD substitution mutant cannot be cleaved by caspase 8
-
-
?
FLIPL protein + H2O
?
-
processing of free FLIPL by caspase-8, FLIPL cleavage increases the recruitment of caspase-8
-
-
?
procaspase-3 + H2O
caspase-3 + ?
-
in some cells, active caspase-8 is sufficient to activate caspase-3 directly. In other cells, however, caspase-8 indirectly mediates caspase-3 activation by cleaving the proapoptotic Bcl-2 family member Bid, which induces mitochondrial cytochrome c release
-
-
?
procaspase-3 + H2O
caspase-3 + ?
-
the cleavage sequence in procaspase-3, catalytically inactive C285A mutant, for caspase-8 is IETD/S
-
-
?
additional information
?
-
the enzyme is indispensable for Fas-mediated apoptotic signaling
-
-
?
additional information
?
-
-
the enzyme is indispensable for Fas-mediated apoptotic signaling
-
-
?
additional information
?
-
-
FLICE is the first in a cascade of ICE-like proteases activated by CD95. Active FLICE is released into the cytosol, where it can activate a cascade of ICE-like proteases
-
-
?
additional information
?
-
-
caspase-8 is dispensable for B-cell development, but its loss in B cells results in attenuated antibody production upon in vivo viral infection. Important role for caspase-8 in maintaining B-cell survival following stimulation of the Toll-like receptor (TLR)2, -3, and -4. In response to TLR4 stimulation, caspase-8 is recruited to a complex containing IKKalphabeta, and its loss results in delayed NFkappaB nuclear translocation and impaired NFkappaB transcriptional activity. Caspase-8 is required forTLRsignaling and in the regulation of NFkappaB function
-
-
?
additional information
?
-
-
caspase-8 participates in regulation of the cellular response to infection and injury. It does so by affecting various cellular functions, including cell death, cell proliferation, and induction of inflammation
-
-
?
additional information
?
-
-
TLR2- and caspase-8-mediated microglial apoptosis constitutes an autoregulatory mechanism that limits group B Streptococcus-induced overactivation of the innate immune system in the central nervous system
-
-
?
additional information
?
-
-
apoptosis in ischemic hearts occurs through the receptor-mediated extrinsic caspase-8 apoptotic pathway as opposed to the mitochondrial caspase-3 pathway, overview
-
-
?
additional information
?
-
-
apoptotic cell deathin LM3 cells is characterized by the activation of caspase-8, -9 and -3, by an increment in the expression levels of the proapoptotic protein Bax and by the release of cytochrome c to cytosol
-
-
?
additional information
?
-
-
caspase-3 is an initiator caspase. Increased caspase-8 activation is involved in initiation of apoptosis, inhibition of caspase-8 impairs Leptospira interrogans-induced caspase-3 and -6 activation, as well as PARP and lamin A/C cleavage and apoptosis, overview. Leptospira interrogans-induced apoptosis in macrophages is mediated by caspase-3 and -6 activation through a FADDcaspase-8-dependent pathway, independently of mitochondrial cytochrome ccaspase-9-dependent signaling, regulation, overview
-
-
?
additional information
?
-
-
caspase-8 acts in apoptosis via the death receptor pathway
-
-
?
additional information
?
-
-
caspase-8 is a executioner or downstream caspase. Apoptosis induced by PBOX-21/STI571 results in activation of caspase-8, cleavage of PARP and Bcl-2, upregulation of the pro-apoptotic protein Bim and a downregulation of Bcr-Abl, important role for caspase-8 in the apoptotic pathway, overview
-
-
?
additional information
?
-
-
caspase-8 is a pro-apoptotic caspase, whose expression is increased in the orbito-frontal cortex 14 days after spared nerve injury of the sciatic nerve, prevented by ozone, regulation, overview
-
-
?
additional information
?
-
-
caspase-8 is involved in apoptosis, ischemia upregulates cytoplasmic adaptor protein Fas-associated Fas and Fas-associated death domain, FADD, expression, and increases caspase-8 and -3 activities in ovariectomy female mouse cortex, which are significantly attenuated by estradiol
-
-
?
additional information
?
-
-
mRNA and protein level of caspase-8 is closely related to cell apoptosis by a death ligand/receptor-dependent apoptosis pathway, increased by L-carnitine treatment, overview
-
-
?
additional information
?
-
-
caspase-8 performs self-cleavage to give the processed active dimer. Within the caspase-8/FLIPL heterodimer, caspase-8 prefers to process FLIPL over itself
-
-
?
additional information
?
-
-
pro-caspase-6, linker, is a poor substrate fpr caspase-8
-
-
?
additional information
?
-
-
the substrate cleft is closed in the monomeric zymogen, whereas the cleft is accessible for substrate binding in both dimers, binding structure, overview
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
CYLD + H2O
CYLDp25 + ?
-
key substrate processed by caspase 8 to block necrosis, CYLD is a key requirement for necrosis of L929 fibrosarcoma cells
-
-
?
FLIPL protein + H2O
?
-
processing of free FLIPL by caspase-8, FLIPL cleavage increases the recruitment of caspase-8
-
-
?
procaspase-3 + H2O
caspase-3 + ?
-
in some cells, active caspase-8 is sufficient to activate caspase-3 directly. In other cells, however, caspase-8 indirectly mediates caspase-3 activation by cleaving the proapoptotic Bcl-2 family member Bid, which induces mitochondrial cytochrome c release
-
-
?
additional information
?
-
the enzyme is indispensable for Fas-mediated apoptotic signaling
-
-
?
additional information
?
-
-
the enzyme is indispensable for Fas-mediated apoptotic signaling
-
-
?
additional information
?
-
-
FLICE is the first in a cascade of ICE-like proteases activated by CD95. Active FLICE is released into the cytosol, where it can activate a cascade of ICE-like proteases
-
-
?
additional information
?
-
-
caspase-8 is dispensable for B-cell development, but its loss in B cells results in attenuated antibody production upon in vivo viral infection. Important role for caspase-8 in maintaining B-cell survival following stimulation of the Toll-like receptor (TLR)2, -3, and -4. In response to TLR4 stimulation, caspase-8 is recruited to a complex containing IKKalphabeta, and its loss results in delayed NFkappaB nuclear translocation and impaired NFkappaB transcriptional activity. Caspase-8 is required forTLRsignaling and in the regulation of NFkappaB function
-
-
?
additional information
?
-
-
caspase-8 participates in regulation of the cellular response to infection and injury. It does so by affecting various cellular functions, including cell death, cell proliferation, and induction of inflammation
-
-
?
additional information
?
-
-
TLR2- and caspase-8-mediated microglial apoptosis constitutes an autoregulatory mechanism that limits group B Streptococcus-induced overactivation of the innate immune system in the central nervous system
-
-
?
additional information
?
-
-
apoptosis in ischemic hearts occurs through the receptor-mediated extrinsic caspase-8 apoptotic pathway as opposed to the mitochondrial caspase-3 pathway, overview
-
-
?
additional information
?
-
-
apoptotic cell deathin LM3 cells is characterized by the activation of caspase-8, -9 and -3, by an increment in the expression levels of the proapoptotic protein Bax and by the release of cytochrome c to cytosol
-
-
?
additional information
?
-
-
caspase-3 is an initiator caspase. Increased caspase-8 activation is involved in initiation of apoptosis, inhibition of caspase-8 impairs Leptospira interrogans-induced caspase-3 and -6 activation, as well as PARP and lamin A/C cleavage and apoptosis, overview. Leptospira interrogans-induced apoptosis in macrophages is mediated by caspase-3 and -6 activation through a FADDcaspase-8-dependent pathway, independently of mitochondrial cytochrome ccaspase-9-dependent signaling, regulation, overview
-
-
?
additional information
?
-
-
caspase-8 acts in apoptosis via the death receptor pathway
-
-
?
additional information
?
-
-
caspase-8 is a executioner or downstream caspase. Apoptosis induced by PBOX-21/STI571 results in activation of caspase-8, cleavage of PARP and Bcl-2, upregulation of the pro-apoptotic protein Bim and a downregulation of Bcr-Abl, important role for caspase-8 in the apoptotic pathway, overview
-
-
?
additional information
?
-
-
caspase-8 is a pro-apoptotic caspase, whose expression is increased in the orbito-frontal cortex 14 days after spared nerve injury of the sciatic nerve, prevented by ozone, regulation, overview
-
-
?
additional information
?
-
-
caspase-8 is involved in apoptosis, ischemia upregulates cytoplasmic adaptor protein Fas-associated Fas and Fas-associated death domain, FADD, expression, and increases caspase-8 and -3 activities in ovariectomy female mouse cortex, which are significantly attenuated by estradiol
-
-
?
additional information
?
-
-
mRNA and protein level of caspase-8 is closely related to cell apoptosis by a death ligand/receptor-dependent apoptosis pathway, increased by L-carnitine treatment, overview
-
-
?
additional information
?
-
-
caspase-8 performs self-cleavage to give the processed active dimer. Within the caspase-8/FLIPL heterodimer, caspase-8 prefers to process FLIPL over itself
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
benzyloxycarbonyl-valyl-alanyl-aspartic acid (O-methyl)-fluoro-methylketone
-
2'-nitroflavone
-
inhibits caspases and tumor cell growth in diverse tissues, overview
CrmA
-
inhibits caspase 8, while mutant CrmAD303A is unable to prevent cleavage of CYLD
-
N-carbobenzyloxy-Ile-Glu(OMe)-Thr-Asp(OMe) fluoromethyl ketone
-
caspase-8 inhibition inhibits apoptosis
N-carbobenzyloxy-IETD-fluoromethyl ketone
-
a caspase-8 imhibitor, reduces the apoptotic rate in LAMA84 cells by about 50%, and prevents pro-caspase-8 cleavage
N-carbobenzyloxy-IETD-fluoromethyl ketone
-
effects on the activation of caspase-8 through cell infection with Leptospira interrogans
Z-VAD-fluoromethylketone
-
i.e. benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone
additional information
activity decreases in aged oocytes, compared to young ones
-
additional information
-
activity decreases in aged oocytes, compared to young ones
-
additional information
-
interleukin-1 does not downregulate caspase-8 expression, but reduces apoptosis within the gastrointestinal crypts
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
CD95
-
FLICE is the first in a cascade of ICE-like proteases activated by CD95. This activation requires a functional CD95 disc
-
FLIPL protein
-
a catalytically defective caspase-8 paralogue, can interact with caspase-8 to activate its catalytic function
-
additional information
-
active caspase-8 is upregulated under irradiation stress, and interleukin-1 does not prevent it when used in pretreatment, overview
-
additional information
-
caspase-8 expression is increased in the orbito-frontal cortex 14 days after spared nerve injury of the sciatic nerve, prevented by ozone
-
additional information
-
caspase-8 expression is induced by Fas, and L-carnitine induces Fas and caspase-8
-
additional information
-
caspase-8 is induced in brain by cerebral ischemia. Upon activation, the cytoplasmic adaptor protein Fas-associated death domain associates with the death domain of Fas, followed by recruitment and activation of caspase-8
-
additional information
-
Leptospira interrogans induces apoptosis in macrophages and hepatocytes via caspase-8- and caspase-3-dependent pathways
-
additional information
-
no induction or activation of caspase-8 by cordycepin in MA-10 mouse Leydig tumor cells, overview
-
additional information
-
PBOX-21/STI571 induces activation of caspase-8 leading to aopotosis
-
additional information
-
caspase-8 activation involves dimerization and subsequent interdomain autoprocessing of caspase-8 zymogens, mechanism, overview. The inactive caspase-8 paralogue FLIPL is able to activate caspase-8 by heterodimerization
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
caspase-8 is developmentally regulated, expression level at 9.5 days is approximately twofold higher than at 17.5 days
-
cleaved caspase-8 is detected in apoptotic cells in the adrenal gland
-
caspase-8 is dispensable for B-cell development, but its loss in B cells results in attenuated antibody production upon in vivo viral infection. Important role for caspase-8 in maintaining B-cell survival following stimulation of the Toll-like receptor (TLR)2, -3, and -4
-
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
-
caspase-8 expression is increased in the orbito-frontal cortex 14 days after spared nerve injury of the sciatic nerve, prevented by ozone
additional information
-
caspase-8 deficiency in hepatocytes facilitates infection of the liver by Listeria monocytogenes, attenuates the hepatocyte proliferation wave during the first 48 hours after partial hepatectomy and, depending on the genetic background of the mice, prompts a chronic inflammatory response to the hepatectomy, as a result of which the proliferation of hepatocytes, although initially suppressed, might later be persistently enhanced, resulting in significant hepatomegaly
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
failure to express caspase-8 has no effect on the life-span of dendritic cells but instead leads to an enhanced intrinsic activation and subsequently more mature and autoreactive lymphocytes. Mice with conditional deletion of caspase-8 in DCs develop a chronic systemic autoimmune disease
physiological function
caspase-8 acts as a molecular rheostat to limit RIPK1- and MyD88-mediated dendritic cell activation
evolution
-
initiator and executioner caspases, the pro-apoptotic members of the caspase family are subdivided in the initiators of apoptosis and the executioners of apoptosis. Caspase-18 and the ancestor of -8 and -10 called caspase-810 in this schematic are still found in fishes. Later on in evolution, caspase-8 and -10 branched off from caspase-810
malfunction
physiological function
additional information
-
FLIPL, a catalytically defective caspase-8 paralog, can interact with caspase-8 to activate its catalytic function. The caspase-8/FLIPL heterodimer has a restricted substrate repertoire and does not induce apoptosis. Caspase-8 heterodimerized with FLIPL prevents the receptor interacting kinases RIPK1 and -3 from executing the form of cell death known as necroptosis
malfunction
-
loss of caspase 8 prevents CYLD degradation, resulting in necrotic death. Mutation of the caspase 8 processing site on the substrate converts a pro-survival response to necrotic death without the need for caspase 8 inhibition
malfunction
-
mice deficient in caspase-8 in basal epidermal keratinocytes suffer from chronic skin inflammation, as an apparent consequence of IRF3 hyper-activation. Catalytically active caspase-8 is required to rescue the lymphocyte development in caspase-8 deficient mice. The developmental phenotype observed in the caspase-8 knockout mouse is shared with both the FLIPL knockout and the FADD knockout
physiological function
-
neuronal death in Tg(DELTACR) mice is not accompanied by activation of caspase-8
physiological function
-
the Fas-associated protein with a death domain and subsequent activated caspase-8 are responsible for double-stranded RNA-dependent protein kinase-induced apoptosis in recombinant virus-infected cells
physiological function
-
caspase 8 inhibits programmed necrosis by processing CYLD. Suppression of necrotic cell death by caspase 8 requires its catalytic activity but not the autocleavage essential for apoptosis. CYLD is cleaved by caspase 8 to promote survival
physiological function
-
caspase-8, the initiator of extrinsically-triggered apoptosis, also has important functions in cellular activation and differentiation downstream of a variety of cell surface receptors. The heterodimer of caspase-8 with the long isoform of cellular FLIP, FLIPL, fulfills these pro-survival functions of caspase-8. Caspase-8 has important functions in survival and development, caspase-8 activation not only triggers apoptosis but is also essential for embryonic development. Tissue specific knockout of caspase-8 revealed an essential role for this caspase in the development of a variety of tissues,most notably the endothelial cells of the heart and vascular system, lymphocytes and monocytes. Caspase-8 in programmed necrosis, detailed overview
physiological function
-
FADD-dependent formation of heterodimers between caspase-8 and FLIPL mediates the developmental role of caspase-8. The catalytic domain of caspase-8 is crucial for its activity in the context of activation by homodimerization. Mechanism of caspase-8 functional divergence in apoptotic and non-apoptotic pathways, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). CASP8_MOUSE
480
0
55357
Swiss-Prot
other Location (Reliability: 3)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
monomer
-
inactive zymogen, the monomeric form of caspase-8 has a typical caspase fold, consisting of a six-stranded beta sheet formed by five parallel and one anti-parallel beta strand, overview
additional information
-
caspases can only be active as dimers, since neither the active site dyad nor the substrate pocket can be formed in the monomeric form, structure analysis and comparison of caspase-8 monomeric zymogen and the substrate-bound, fully-processed, caspase-8 dimer, overview
dimer
-
caspase-8 activation involves dimerization and subsequent interdomain autoprocessing of caspase-8 zymogens, overview. The catalytic domain of caspase-8 is crucial for its activity in the context of activation by homodimerization
dimer
-
processed active enzyme, during dimerization, a loop containing a small helix translocates from the active site
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
proteolytic modification
-
caspase-8 activation involves dimerization and subsequent interdomain autoprocessing of caspase-8 zymogens
proteolytic modification
-
caspase-8 is activated at the DISC, downstream of death-receptor signaling. Mouse caspase-8 only has one cleavage site in the ubunit linker
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
homodimerization fully activates both mature caspase-8 and the site-2 mutant, but fails to activate variants containing noncleavable mutations at site-1. The caspase-8 site-1 mutant is incapable of binding Z-VAD-fluoromethylketone when introduced into caspase-8-null NB7 cells, and stimulated to die via the extrinsic pathway. Elimination of the autoprocessing site of caspase-8 abrogates its pro-apoptotic function while leaving its proliferative function intact. Non-cleavable caspase-8-FLIPL heterodimer has attenuated activity on most apoptotic substrates, but shows high activity on HDAC-7
additional information
-
transfection of wild-type MEFs with two different Casp8-targeting RNAi oligonucleotides leads to knockdown of caspase 8
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant N-terminal His8-tagged FK506-binding protein-caspase-8 fusion protein mutants from Escherichia coli BL21(DE3) by nickel affinity and anion exchange chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of FK506-binding protein-caspase-8 fusion protein mutants in Escherichia coli BL21(DE3) as N-terminal His-tagged constructs using pET28b. Co-expression of caspase-8 and FLIPL in HeLa cells, the active-site cleft is restricted in caspase-8-FLIPL heterodimers
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
alphavirus Semliki Forest virus and its derived vectors induce apoptosis in mammalian cells followed by the activation of caspase-8
-
the activity of caspase-8 increases about 50-60% in amyloid-beta peptide-treated cells compared to untreated cells
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
caspase-8 activity prevents type 2 cytokinine responses and is required for protective T cell-mediated immunity against Trypanosoma cruzi infection
medicine
caspase-8 is potentially metastasis promoting in other tumor types than neuroblastoma because it stimulates cell migration
medicine
clinical therapies involving caspase inhibitors may arrest apoptosis, but also have the effect of promoting autophagic cell death
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Sakamaki, K.; Tsukumo, S.I.; Yonehara, S.
Molecular cloning and characterization of mouse caspase-8
Eur. J. Biochem.
253
399-405
1998
Mus musculus (O89110), Mus musculus, Mus musculus 129/SvJ (O89110)
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
van de Craen, M.; Berx, G.; van den Brande, I.; Fiers, W.; Declercq, W.; Vandenabeele, P.
Proteolytic cleavage of beta-catenin by caspases: an in vitro analysis
FEBS Lett.
458
167-170
1999
Mus musculus
Helfer, B.; Boswell, B.C.; Finlay, D.; Cipres, A.; Vuori, K.; Bong Kang, T.; Wallach, D.; Dorfleutner, A.; Lahti, J.M.; Flynn, D.C.; Frisch, S.M.
Caspase-8 promotes cell motility and calpain activity under nonapoptotic conditions
Cancer Res.
66
4273-4278
2006
Mus musculus (O89110)
Dohrman, A.; Kataoka, T.; Cuenin, S.; Russell, J.Q.; Tschopp, J.; Budd, R.C.
Cellular FLIP (long form) regulates CD8+ T cell activation through caspase-8-dependent NF-kappa B activation
J. Immunol.
174
5270-5278
2005
Mus musculus (O89110)
Silva, E.M.; Guillermo, L.V.; Ribeiro-Gomes, F.L.; De Meis, J.; Pereira, R.M.; Wu, Z.; Calegari-Silva, T.C.; Seabra, S.H.; Lopes, U.G.; Siegel, R.M.; Dosreis, G.A.; Lopes, M.F.
Caspase-8 activity prevents type 2 cytokine responses and is required for protective T cell-mediated immunity against Trypanosoma cruzi infection
J. Immunol.
174
6314-6321
2005
Mus musculus (O89110), Mus musculus
Beisner, D.R.; Chen, I.L.; Kolla, R.V.; Hoffmann, A.; Hedrick, S.M.
Cutting edge: innate immunity conferred by B cells is regulated by caspase-8
J. Immunol.
175
3469-3473
2005
Mus musculus (O89110)
Yu, L.; Alva, A.; Su, H.; Dutt, P.; Freundt, E.; Welsh, S.; Baehrecke, E.H.; Lenardo, M.J.
Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8
Science
304
1500-1502
2004
Mus musculus (O89110)
Papandile, A.; Tyas, D.; OMalley, D.M.; Warner, C.M.
Analysis of caspase-3, caspase-8 and caspase-9 enzymatic activities in mouse oocytes and zygotes
Zygote
12
57-64
2004
Mus musculus (O89110), Mus musculus
Liadis, N.; Salmena, L.; Kwan, E.; Tajmir, P.; Schroer, S.A.; Radziszewska, A.; Li, X.; Sheu, L.; Eweida, M.; Xu, S.; Gaisano, H.Y.; Hakem, R.; Woo, M.
Distinct in vivo roles of caspase-8 in beta-cells in physiological and diabetes models
Diabetes
56
2302-2311
2007
Mus musculus
Ben Moshe, T.; Barash, H.; Kang, T.B.; Kim, J.C.; Kovalenko, A.; Gross, E.; Schuchmann, M.; Abramovitch, R.; Galun, E.; Wallach, D.
Role of caspase-8 in hepatocyte response to infection and injury in mice
Hepatology
45
1014-1024
2007
Mus musculus
Bae, S.; Ha, T.S.; Yoon, Y.; Lee, J.; Cha, H.J.; Yoo, H.; Choe, T.B.; Li, S.; Sohn, I.; Kim, J.Y.; Kim, C.S.; Jin, H.O.; Lee, H.C.; Park, I.C.; Kim, C.S.; Jin, Y.W.; Ahn, S.K.
Genome-wide screening and identification of novel proteolytic cleavage targets of caspase-8 and -10 in vitro
Int. J. Mol. Med.
21
381-386
2008
Mus musculus
Lemmers, B.; Salmena, L.; Bidere, N.; Su, H.; Matysiak-Zablocki, E.; Murakami, K.; Ohashi, P.S.; Jurisicova, A.; Lenardo, M.; Hakem, R.; Hakem, A.
Essential role for caspase-8 in Toll-like receptors and NFkappaB signaling
J. Biol. Chem.
282
7416-7423
2007
Mus musculus
Lehnardt, S.; Wennekamp, J.; Freyer, D.; Liedtke, C.; Krueger, C.; Nitsch, R.; Bechmann, I.; Weber, J.R.; Henneke, P.
TLR2 and caspase-8 are essential for group B Streptococcus-induced apoptosis in microglia
J. Immunol.
179
6134-6143
2007
Mus musculus
Fan, J.P.; Kim, H.S.; Han, G.D.
Induction of apoptosis by L-carnitine through regulation of two main pathways in Hepa1c1c 7 cells
Amino Acids
36
365-372
2009
Mus musculus
Johnke, R.M.; Smith, E.S.; Cariveau, M.J.; Evans, M.J.; Kilburn, J.M.; Bakken, N.T.; Nangami, G.N.
Radioprotection of murine gastrointestinal epithelium by interleukin-1alpha involves down-regulation of the apoptotic response
Anticancer Res.
28
3601-3607
2009
Mus musculus, Mus musculus C57BL/6
Calafat, M.; Larocca, L.; Roca, V.; Hauk, V.; Pregi, N.; Nesse, A.; Perez Leiros, C.
Vasoactive intestinal peptide inhibits tumor necrosis factor-alpha-induced apoptotic events in acinar cells from non-obese diabetic mice submandibular glands
Arthritis Res. Ther.
11
R53
2009
Mus musculus
Fuccio, C.; Luongo, C.; Capodanno, P.; Giordano, C.; Scafuro, M.A.; Siniscalco, D.; Lettieri, B.; Rossi, F.; Maione, S.; Berrino, L.
A single subcutaneous injection of ozone prevents allodynia and decreases the over-expression of pro-inflammatory caspases in the orbito-frontal cortex of neuropathic mice
Eur. J. Pharmacol.
603
42-49
2009
Mus musculus
Jen, C.Y.; Lin, C.Y.; Leu, S.F.; Huang, B.M.
Cordycepin induced MA-10 mouse Leydig tumor cell apoptosis through caspase-9 pathway
Evid. Based. Complement Alternat. Med.
2009
1-10
2009
Mus musculus
Jia, J.; Guan, D.; Zhu, W.; Alkayed, N.J.; Wang, M.M.; Hua, Z.; Xu, Y.
Estrogen inhibits Fas-mediated apoptosis in experimental stroke
Exp. Neurol.
215
48-52
2009
Mus musculus
French, C.J.; Spees, J.L.; Zaman, A.K.; Taatjes, D.J.; Sobel, B.E.
The magnitude and temporal dependence of apoptosis early after myocardial ischemia with or without reperfusion
FASEB J.
23
1177-1185
2009
Mus musculus, Mus musculus C57BL6
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
Cardenas, M.G.; Zotta, E.; Marder, M.; Roguin, L.P.
In vitro induction of apoptosis and in vivo effects of a flavone nitroderivative in murine mammary adenocarcinoma cells
Int. J. Cancer
125
222-228
2009
Mus musculus, Mus musculus BALB/c
Christensen, H.M.; Dikranian, K.; Li, A.; Baysac, K.C.; Walls, K.C.; Olney, J.W.; Roth, K.A.; Harris, D.A.
A highly toxic cellular prion protein induces a novel, nonapoptotic form of neuronal death
Am. J. Pathol.
176
2695-2706
2010
Mus musculus
Esaki, S.; Goshima, F.; Katsumi, S.; Watanabe, D.; Ozaki, N.; Murakami, S.; Nishiyama, Y.
Apoptosis induction after herpes simplex virus infection differs according to cell type in vivo
Arch. Virol.
155
1235-1245
2010
Mus musculus
Eley, H.L.; Russell, S.T.; Tisdale, M.J.
Mechanism of activation of dsRNA-dependent protein kinase (PKR) in muscle atrophy
Cell. Signal.
22
783-790
2010
Mus musculus
Couturier, J.; Morel, M.; Pontcharraud, R.; Gontier, V.; Fauconneau, B.; Paccalin, M.; Page, G.
Interaction of double-stranded RNA-dependent protein kinase (PKR) with the death receptor signaling pathway in amyloid beta (Abeta)-treated cells and in APPSLPS1 knock-in mice
J. Biol. Chem.
285
1272-1282
2010
Mus musculus
Barry, G.; Fragkoudis, R.; Ferguson, M.C.; Lulla, A.; Merits, A.; Kohl, A.; Fazakerley, J.K.
Semliki Forest virus induced endoplasmic reticulum stress accelerates apoptotic death of mammalian cells
J. Virol.
84
7369-7377
2010
Mus musculus
Gonzalvez, F.; Pariselli, F.; Jalmar, O.; Dupaigne, P.; Sureau, F.; Dellinger, M.; Hendrickson, E.A.; Bernard, S.; Petit, P.X.
Mechanistic issues of the interaction of the hairpin-forming domain of tBid with mitochondrial cardiolipin
PLoS ONE
5
e9342
2010
Mus musculus
Pop, C.; Oberst, A.; Drag, M.; Van Raam, B.J.; Riedl, S.J.; Green, D.R.; Salvesen, G.S.
FLIP(L) induces caspase 8 activity in the absence of interdomain caspase 8 cleavage and alters substrate specificity
Biochem. J.
433
447-457
2011
Mus musculus
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
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
Cuda, C.M.; Misharin, A.V.; Gierut, A.K.; Saber, R.; Haines, G.K.; Hutcheson, J.; Hedrick, S.M.; Mohan, C.; Budinger, G.S.; Stehlik, C.; Perlman, H.
Caspase-8 acts as a molecular rheostat to limit RIPK1- and MyD88-mediated dendritic cell activation
J. Immunol.
192
5548-5560
2014
Mus musculus (O89110)
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