◀ Back to CASP8
CASP8 — RIPK1
Pathways - manually collected, often from reviews:
-
BioCarta induction of apoptosis through dr3 and dr4/5 death receptors:
DR3/TRADD/FADD/TRAF2/RIP/Caspase 8/Caspase 10/APO-3L complex (TNFRSF25-TRADD-FADD-TRAF2-RIPK1-CASP8-CASP10-TNFSF12)
→
APO-3L (TNFSF12)
(modification, collaborate)
-
BioCarta induction of apoptosis through dr3 and dr4/5 death receptors:
DR3/TRADD/FADD/TRAF2/RIP/Caspase 8/Caspase 10/APO-3L complex (TNFRSF25-TRADD-FADD-TRAF2-RIPK1-CASP8-CASP10-TNFSF12)
→
DR3/TRADD/FADD/TRAF2/RIP/Caspase 8/Caspase 10 complex (TNFRSF25-TRADD-FADD-TRAF2-RIPK1-CASP8-CASP10)
(modification, collaborate)
-
BioCarta induction of apoptosis through dr3 and dr4/5 death receptors:
APO-3L (TNFSF12)
→
DR3/TRADD/FADD/TRAF2/RIP/Caspase 8/Caspase 10 complex (TNFRSF25-TRADD-FADD-TRAF2-RIPK1-CASP8-CASP10)
(modification, collaborate)
-
BioCarta tnfr1 signaling pathway:
TNF-alpha/TNF R1/RIP/RAIDD/MADD/TRADD/TRAF2/cIAP complex (TNF-CRADD-TRAF2-BIRC3-TNFRSF1A-MADD-RIPK1-TRADD)
→
FADD/Caspase 8 complex (CASP8-FADD)
(modification, activates)
-
BioCarta tnfr1 signaling pathway:
TNF-alpha/TNF R1/RIP/RAIDD/MADD/TRADD/TRAF2/cIAP complex (TNF-CRADD-TRAF2-BIRC3-TNFRSF1A-MADD-RIPK1-TRADD)
→
Caspase 8 (CASP8)
(modification, activates)
-
BioCarta induction of apoptosis through dr3 and dr4/5 death receptors:
DR3/TRADD/FADD/TRAF2/RIP/Caspase 8/Caspase 10/APO-3L complex (TNFRSF25-TRADD-FADD-TRAF2-RIPK1-CASP8-CASP10-TNFSF12)
→
Caspase 3 (CASP3)
(modification, activates)
-
BioCarta induction of apoptosis through dr3 and dr4/5 death receptors:
DR3/TRADD/FADD/TRAF2/RIP/Caspase 8/Caspase 10/APO-3L complex (TNFRSF25-TRADD-FADD-TRAF2-RIPK1-CASP8-CASP10-TNFSF12)
→
Caspase 3 (active) (CASP3)
(modification, activates)
-
BioCarta ceramide signaling pathway:
FADD/Caspase 8 complex (CASP8-FADD)
→
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD complex (TRADD-MADD-BIRC3-RIPK1-TRAF2-CRADD-TNFRSF1A-TNF)
(modification, collaborate)
-
BioCarta induction of apoptosis through dr3 and dr4/5 death receptors:
DR3/TRADD/FADD/TRAF2/RIP/Caspase 8/Caspase 10/APO-3L complex (TNFRSF25-TRADD-FADD-TRAF2-RIPK1-CASP8-CASP10-TNFSF12)
→
MAP3K14
(modification, activates)
-
NCI Pathway Database HIV-1 Nef: Negative effector of Fas and TNF-alpha:
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP/cIAP2/TRAF1/TRAF2/Ask1/RAIDD complex (TNFRSF1A-CASP2-TNF-FADD-TRADD-RIPK1-MAP3K5-TRAF1-TRAF2-BIRC3-CRADD)
→
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG complex (FASLG-CASP8-MAP3K5-FAS-DAXX-FADD)
(modification, activates)
Micheau et al., Cell 2003, Yang et al., Cell 1997, Saitoh et al., EMBO J 1998, Chang et al., Science 1998
-
NCI Pathway Database TRAIL signaling pathway:
Caspase 8 (tetramer) complex (CASP8)
→
RIP (RIPK1)
(modification, activates)
Lin et al., Genes Dev 1999*, Harper et al., J Biol Chem 2001
-
NCI Pathway Database Ceramide signaling pathway:
FADD/Caspase 8 complex (CASP8-FADD)
→
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP/TRAF2/RAIDD complex (TRADD-MADD-BIRC3-RIPK1-TRAF2-CRADD-TNFRSF1A-TNF)
(modification, collaborate)
Boldin et al., Cell 1996, Muzio et al., Cell 1996
Evidence: assay
-
NCI Pathway Database TNF receptor signaling pathway :
Caspase 8 (CASP8)
→
sTNF-alpha/TNFR1A/TRADD/RIP/TRAF2/cIAP1/cIAP2 complex (TNFRSF1A-TRADD-RIPK1-TRAF2-BIRC2-BIRC3-TNF)
(modification, collaborate)
Schneider-Brachert et al., Immunity 2004, Schneider-Brachert et al., J Clin Invest 2006, Boldin et al., Cell 1996
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database TNF receptor signaling pathway :
sTNF-alpha/TNFR1A/TRADD/RIP/TRAF2/cIAP1/cIAP2 complex (TNFRSF1A-TRADD-RIPK1-TRAF2-BIRC2-BIRC3-TNF)
→
Caspase 8 (tetramer) complex (CASP8)
(modification, inhibits)
Schneider-Brachert et al., Immunity 2004, Schneider-Brachert et al., J Clin Invest 2006, Boldin et al., Cell 1996
Evidence: mutant phenotype, assay, physical interaction
-
Reactome Reaction:
CASP8
→
RIPK1
(reaction)
Wang et al., Proc Natl Acad Sci U S A 2001, Thomas et al., J Biol Chem 2002, Kalai et al., Cell Death Differ 2002, Donepudi et al., Mol Cell 2003, Creagh et al., Immunol Rev 2003, Shikama et al., Eur J Immunol 2003, Micheau et al., Cell 2003, Han et al., J Biol Chem 2004, Kaiser et al., J Immunol 2005, Takahashi et al., J Immunol 2006, Lamkanfi et al., J Cell Biol 2006, Wang et al., Cell 2008*, Maelfait et al., Biochem Pharmacol 2008, Keller et al., Structure 2009, Oberst et al., J Biol Chem 2010, Tenev et al., Mol Cell 2011, Feoktistova et al., Mol Cell 2011, Estornes et al., Cell Death Differ 2012
-
Reactome Reaction:
CASP8
→
RIPK1
(direct_complex)
Kalai et al., Cell Death Differ 2002, Creagh et al., Immunol Rev 2003, Han et al., J Biol Chem 2004, Kaiser et al., J Immunol 2005, Tenev et al., Mol Cell 2011, Feoktistova et al., Mol Cell 2011, Estornes et al., Cell Death Differ 2012
-
Reactome Reaction:
CASP8
→
RIPK1
(indirect_complex)
Donepudi et al., Mol Cell 2003, Micheau et al., Cell 2003, Rushworth et al., Cell cycle (Georgetown, Tex.) 2008*, Wang et al., Cell 2008*, Seal et al., Exp Hematol 2008*, Vittori et al., Cell Biol Int 2010*
-
WikiPathways RIG-I-like Receptor Signaling:
Complex of FADD-RIPK1
→
Complex of CASP8-CASP10
(activation)
-
WikiPathways Apoptosis:
RIPK1/TRADD/FADD
→
CASP8
(activation)
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
-
IRef Biogrid Interaction:
RIPK1
—
CASP8
(physical association, affinity chromatography technology)
Rébé et al., Blood 2007
-
IRef Biogrid Interaction:
RIPK1
—
CASP8
(physical association, affinity chromatography technology)
Lee et al., Nature communications 2012
-
IRef Biogrid Interaction:
RIPK1
—
CASP8
(physical association, affinity chromatography technology)
Feoktistova et al., Cell cycle (Georgetown, Tex.) 2012*
-
IRef Biogrid Interaction:
RIPK1
—
CASP8
(physical association, affinity chromatography technology)
Chaudhary et al., Oncogene 2000
-
IRef Biogrid Interaction:
RIPK1
—
CASP8
(physical association, affinity chromatography technology)
Oshima et al., Nature 2009*
-
IRef Biogrid Interaction:
RIPK1
—
CASP8
(physical association, affinity chromatography technology)
Cheung et al., Cancer Res 2009*
-
IRef Biogrid Interaction:
RIPK1
—
CASP8
(physical association, affinity chromatography technology)
Knox et al., J Cell Biol 2011*
-
IRef Biogrid Interaction:
RIPK1
—
CASP8
(physical association, affinity chromatography technology)
Kim et al., Cancer Sci 2010*
-
IRef Biogrid Interaction:
RIPK1
—
CASP8
(physical association, affinity chromatography technology)
Tenev et al., Mol Cell 2011
-
IRef Biogrid Interaction:
RIPK1
—
CASP8
(direct interaction, pull down)
Tenev et al., Mol Cell 2011
-
IRef Biogrid Interaction:
RIPK1
—
CASP8
(physical association, affinity chromatography technology)
Mahul-Mellier et al., Cell Death Differ 2012
-
IRef Biogrid Interaction:
RIPK1
—
CASP8
(colocalization, biochemical)
Bellail et al., Cancer Discov 2012
-
IRef Biogrid Interaction:
RIPK1
—
CASP8
(physical association, affinity chromatography technology)
Legarda-Addison et al., Cell Death Differ 2009*
-
IRef Biogrid Interaction:
RIPK1
—
CASP8
(physical association, affinity chromatography technology)
Bellail et al., Cancer Discov 2012
-
IRef Biogrid Interaction:
RIPK1
—
CASP8
(physical association, affinity chromatography technology)
Biton et al., Cell 2011*
-
IRef Biogrid Interaction:
RIPK1
—
CASP8
(physical association, affinity chromatography technology)
Bertrand et al., Mol Cell 2008
-
IRef Biogrid Interaction:
RIPK1
—
CASP8
(physical association, affinity chromatography technology)
Puliyappadamba et al., Cell reports 2013
-
IRef Dip Interaction:
Complex of CASP8-RIPK1-TNFAIP3
(anti bait coimmunoprecipitation)
Oshima et al., Nature 2009*
-
IRef Dip Interaction:
Complex of FADD-CASP8-RIPK1-TNFAIP3
(anti bait coimmunoprecipitation)
Oshima et al., Nature 2009*
-
IRef Dip Interaction:
RIPK1
—
CASP8
(physical association, anti bait coimmunoprecipitation)
Oshima et al., Nature 2009*
-
IRef Hprd Interaction:
RIPK1
—
CASP8
(in vivo)
Lin et al., Genes Dev 1999*, Chaudhary et al., Oncogene 2000, Micheau et al., J Biol Chem 2002*
-
IRef Hprd Interaction:
RIPK1
—
CASP8
(in vitro)
Lin et al., Genes Dev 1999*, Chaudhary et al., Oncogene 2000, Micheau et al., J Biol Chem 2002*
-
IRef Intact Interaction:
Complex of FADD-RIPK1-RIPK3-CASP8
(physical association, anti bait coimmunoprecipitation)
He et al., Cell 2009*
-
IRef Intact Interaction:
Complex of RIPK1-RIPK3-CASP8
(association, anti bait coimmunoprecipitation)
Cho et al., Cell 2009*
-
IRef Intact Interaction:
Complex of CASP8-RIPK1-TNFRSF10A-TNFRSF10B-FADD-CFLAR
(association, anti bait coimmunoprecipitation)
Rébé et al., Blood 2007
-
IRef Intact Interaction:
Complex of CASP8-FADD-RIPK1-BIRC2
(association, anti bait coimmunoprecipitation)
Feoktistova et al., Cell cycle (Georgetown, Tex.) 2012*
-
IRef Intact Interaction:
Complex of TRAF2-RIPK1-TRADD-FADD-CASP8-CFLAR
(association, anti bait coimmunoprecipitation)
Rébé et al., Blood 2007
-
IRef Intact Interaction:
Complex of 17 proteins
(association, anti bait coimmunoprecipitation)
Rébé et al., Blood 2007
-
IRef Intact Interaction:
Complex of TRAF2-TRAF1-TRADD-FADD-CASP8-CFLAR-BIRC2-RIPK1
(association, anti bait coimmunoprecipitation)
Micheau et al., Cell 2003
-
IRef Intact Interaction:
Complex of CASP8-CASP10-CFLAR-TRADD-TRAF2-RIPK1-FADD
(association, anti bait coimmunoprecipitation)
Micheau et al., Cell 2003
-
IRef Intact Interaction:
RIPK1
—
CASP8
(physical association, pull down)
Shikama et al., Eur J Immunol 2003
-
IRef Intact Interaction:
RIPK1
—
CASP8
(physical association, anti bait coimmunoprecipitation)
Micheau et al., Cell 2003
-
IRef Intact Interaction:
RIPK1
—
CASP8
(physical association, anti bait coimmunoprecipitation)
Biton et al., Cell 2011*
-
IRef Intact Interaction:
RIPK1
—
CASP8
(physical association, anti bait coimmunoprecipitation)
Ikner et al., J Biol Chem 2011*
-
IRef Intact Interaction:
Complex of TRADD-RIPK1-CASP8
(association, anti bait coimmunoprecipitation)
Cho et al., Cell 2009*
-
IRef Intact Interaction:
Complex of 31 proteins
(association, anti bait coimmunoprecipitation)
Löder et al., Leukemia 2012*
-
IRef Ophid Interaction:
RIPK1
—
CASP8
(aggregation, interologs mapping)
Brown et al., Bioinformatics 2005
-
IRef Ophid Interaction:
RIPK1
—
CASP8
(aggregation, confirmational text mining)
Chaudhary et al., Oncogene 2000
Text-mined interactions from Literome
Martinet et al., Autophagy 2006
(Atherosclerosis) :
This finding suggests that
caspase inhibition
activates RIP1 which in turn initiates autophagy, although other explanations should be taken into account
Wang et al., Cell 2008
:
RIPK1 is
critical for
caspase-8 activation induced by Smac mimetic but dispensable for that triggered by cycloheximide
Morgan et al., J Immunol 2009
:
Membrane bound Fas ligand
requires RIP1 for efficient activation of
caspase-8 within the death inducing signaling complex
Gentle et al., J Biol Chem 2011
:
After receptor ligation,
RIPK1 not only modulates activation of both canonical and NIK dependent NF-?B, but also
regulates caspase-8 activation and cell death ... After receptor ligation,
RIPK1 not only modulates activation of both canonical and NIK dependent NF-?B, but also
regulates caspase-8 activation and cell death
Löder et al., Leukemia 2012
(Precursor Cell Lymphoblastic Leukemia-Lymphoma) :
Similarly, inhibition of
RIP1 kinase activity by Necrostatin-1 or blockage of TNFa by Enbrel
inhibits IAP inhibitor- and AraC triggered interaction of RIP1, FADD and
caspase-8 and apoptosis
Duprez et al., Immunity 2011
(Cecal Diseases...) :
An additional switch decides, depending on the cellular context, between
caspase dependent apoptosis and
RIP kinase ( RIPK ) -mediated necrosis, also termed necroptosis
Abhari et al., Oncogene 2013
:
RIP1 is
required for the formation of a
RIP1/FADD/caspase-8 complex that drives caspase-8 activation, cleavage of Bid into tBid, mitochondrial outer membrane permeabilization, full activation of caspase-3 and caspase dependent apoptosis
Basit et al., J Biol Chem 2012
(Rhabdomyosarcoma) :
Importantly, knockdown of RIP1 by RNA interference prevented the formation of the
RIP1·FADD·caspase-8 complex and inhibited subsequent
activation of
caspase-8 , -9, and -3 ; loss of mitochondrial membrane potential ; and apoptosis upon treatment with IAP inhibitor and lexatumumab
Kaczmarek et al., Immunity 2013
(Bacterial Infections...) :
Regulated necrosis, termed necroptosis, is negatively regulated by
caspase-8 and is
dependent on the kinase activity of
RIPK1 and RIPK3