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CFLAR — FAS

Pathways - manually collected, often from reviews:

• OpenBEL Selventa BEL large corpus: Complex of CFLAR-KRT18-KRT8-RAF1 → FAS (increases) Gilbert et al., Mol Cell Biol 2004*
  Evidence: c-Flip, along with Raf-1, is part of a K8/K18-immunoisolated complex from wild-type hepatocytes, and Fas stimulation leads to further c-Flip and Raf-1 recruitment in the complex.
• BioCarta hiv-1 nef: negative effector of fas and tnf: FAS/FADD/DAXX/ASK1/Caspase 8/Caspase 8/FAS L complex (FAS-FADD-DAXX-MAP3K5-CASP8-FASLG) → I-FLICE (CFLAR) (modification, activates)
• BioCarta fas signaling pathway (cd95): I-FLICE/RIP2 complex (CFLAR-RIPK2) → FAS L/FAS/DAXX/FADD/FAF1/Caspase 10 complex (FASLG-FAS-DAXX-FADD-FAF1-CASP10) (modification, activates)
  
• NCI Pathway Database FAS (CD95) signaling pathway: FASLG/FAS (trimer)/FADD/FADD/CASP10 p23/17/c-FLIPL p43 complex (FAS-FASLG-FADD-CASP10-CFLAR) → Caspase 10 (CASP10) (modification, collaborate) Wang et al., Proc Natl Acad Sci U S A 2001, Chang et al., EMBO J 2002, Vincenz et al., J Biol Chem 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: FASLG/FAS (trimer)/FADD/FADD/CASP10 p23/17/c-FLIPL p43 complex (FAS-FASLG-FADD-CASP10-CFLAR) → c-FLIP (CFLAR) (modification, collaborate) Wang et al., Proc Natl Acad Sci U S A 2001, Chang et al., EMBO J 2002, Vincenz et al., J Biol Chem 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: FASLG/FAS (trimer)/FADD/FADD/CASP10 p23/17/c-FLIPL p43 complex (FAS-FASLG-FADD-CASP10-CFLAR) → FASLG/FAS (trimer)/FADD/FADD complex (FAS-FASLG-FADD) (modification, collaborate)
  Wang et al., Proc Natl Acad Sci U S A 2001, Chang et al., EMBO J 2002, Vincenz et al., J Biol Chem 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: FASLG/FAS (trimer)/FADD/FADD/CASP10 p23/17/c-FLIPL p43 complex (FAS-FASLG-FADD-CASP10-CFLAR) → FASLG/FAS (trimer)/FADD/FADD/CASP10/CASP10 complex (FAS-FASLG-FADD-CASP10) (modification, collaborate)
  Wang et al., Proc Natl Acad Sci U S A 2001, Chang et al., EMBO J 2002, Vincenz et al., J Biol Chem 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: FASLG/FAS (trimer)/FADD/FADD/CASP10 p23/17/c-FLIPL p43 complex (FAS-FASLG-FADD-CASP10-CFLAR) → Caspase 10 p12 (CASP10) (modification, collaborate) Wang et al., Proc Natl Acad Sci U S A 2001, Chang et al., EMBO J 2002, Vincenz et al., J Biol Chem 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: FASLG/FAS (trimer)/FADD/FADD/CASP10 p23/17/c-FLIPL p43 complex (FAS-FASLG-FADD-CASP10-CFLAR) → c-FLIPL p12 (CFLAR) (modification, collaborate) Wang et al., Proc Natl Acad Sci U S A 2001, Chang et al., EMBO J 2002, Vincenz et al., J Biol Chem 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: c-FLIP (CFLAR) → FASLG/FAS (trimer)/FADD/FADD complex (FAS-FASLG-FADD) (modification, collaborate)
  Wang et al., Proc Natl Acad Sci U S A 2001, Chang et al., EMBO J 2002, Vincenz et al., J Biol Chem 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: c-FLIP (CFLAR) → FASLG/FAS (trimer)/FADD/FADD/CASP10/CASP10 complex (FAS-FASLG-FADD-CASP10) (modification, collaborate)
  Wang et al., Proc Natl Acad Sci U S A 2001, Chang et al., EMBO J 2002, Vincenz et al., J Biol Chem 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: FASLG/FAS (trimer)/FADD/FADD complex (FAS-FASLG-FADD) → c-FLIPL p12 (CFLAR) (modification, collaborate) Wang et al., Proc Natl Acad Sci U S A 2001, Chang et al., EMBO J 2002, Vincenz et al., J Biol Chem 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: FASLG/FAS (trimer)/FADD/FADD/CASP10/CASP10 complex (FAS-FASLG-FADD-CASP10) → c-FLIPL p12 (CFLAR) (modification, collaborate) Wang et al., Proc Natl Acad Sci U S A 2001, Chang et al., EMBO J 2002, Vincenz et al., J Biol Chem 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: c-FLIP (CFLAR) → FASLG/FAS (trimer)/FADD/FADD/RIP complex (FAS-FASLG-FADD-RIPK1) (modification, inhibits)
  Holler et al., Nat Immunol 2000, Geserick et al., J Cell Biol 2009, Stanger et al., Cell 1995, Kischkel et al., EMBO J 1995
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: c-FLIP (CFLAR) → FASLG/FAS (trimer) complex (FAS-FASLG) (modification, inhibits)
  Holler et al., Nat Immunol 2000, Geserick et al., J Cell Biol 2009, Stanger et al., Cell 1995, Kischkel et al., EMBO J 1995
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: cIAP1-2 (BIRC2/BIRC3) → FASLG/FAS (trimer)/FADD/FADD/CFLIP complex (FAS-FASLG-FADD-CFLAR) (modification, inhibits)
  Yeh et al., Immunity 2000, Krueger et al., J Biol Chem 2001, Algeciras-Schimnich et al., Mol Cell Biol 2002, Chang et al., EMBO J 2002, Geserick et al., J Cell Biol 2009, Muzio et al., Cell 1996, Medema et al., EMBO J 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: cIAP1-2 (BIRC2/BIRC3) → FASLG/FAS (trimer)/FADD/FADD/CASP8 p43/c-FLIP p43 complex (FAS-FASLG-FADD-CASP8-CFLAR) (modification, inhibits)
  Yeh et al., Immunity 2000, Krueger et al., J Biol Chem 2001, Algeciras-Schimnich et al., Mol Cell Biol 2002, Chang et al., EMBO J 2002, Geserick et al., J Cell Biol 2009, Muzio et al., Cell 1996, Medema et al., EMBO J 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: Caspase 8 (CASP8) → FASLG/FAS (trimer)/FADD/FADD/CFLIP complex (FAS-FASLG-FADD-CFLAR) (modification, collaborate)
  Yeh et al., Immunity 2000, Krueger et al., J Biol Chem 2001, Algeciras-Schimnich et al., Mol Cell Biol 2002, Chang et al., EMBO J 2002, Geserick et al., J Cell Biol 2009, Muzio et al., Cell 1996, Medema et al., EMBO J 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: Caspase 8 (CASP8) → FASLG/FAS (trimer)/FADD/FADD/CASP8 p43/c-FLIP p43 complex (FAS-FASLG-FADD-CASP8-CFLAR) (modification, collaborate)
  Yeh et al., Immunity 2000, Krueger et al., J Biol Chem 2001, Algeciras-Schimnich et al., Mol Cell Biol 2002, Chang et al., EMBO J 2002, Geserick et al., J Cell Biol 2009, Muzio et al., Cell 1996, Medema et al., EMBO J 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: FASLG/FAS (trimer)/FADD/FADD/CASP8/CASP8 complex (FAS-FASLG-FADD-CASP8) → c-FLIP (CFLAR) (modification, collaborate) Yeh et al., Immunity 2000, Krueger et al., J Biol Chem 2001, Algeciras-Schimnich et al., Mol Cell Biol 2002, Chang et al., EMBO J 2002, Geserick et al., J Cell Biol 2009, Muzio et al., Cell 1996, Medema et al., EMBO J 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: FASLG/FAS (trimer)/FADD/FADD/CASP8/CASP8 complex (FAS-FASLG-FADD-CASP8) → FASLG/FAS (trimer)/FADD/FADD/CFLIP complex (FAS-FASLG-FADD-CFLAR) (modification, collaborate)
  Yeh et al., Immunity 2000, Krueger et al., J Biol Chem 2001, Algeciras-Schimnich et al., Mol Cell Biol 2002, Chang et al., EMBO J 2002, Geserick et al., J Cell Biol 2009, Muzio et al., Cell 1996, Medema et al., EMBO J 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: FASLG/FAS (trimer)/FADD/FADD/CASP8/CASP8 complex (FAS-FASLG-FADD-CASP8) → FASLG/FAS (trimer)/FADD/FADD/CASP8 p43/c-FLIP p43 complex (FAS-FASLG-FADD-CASP8-CFLAR) (modification, collaborate)
  Yeh et al., Immunity 2000, Krueger et al., J Biol Chem 2001, Algeciras-Schimnich et al., Mol Cell Biol 2002, Chang et al., EMBO J 2002, Geserick et al., J Cell Biol 2009, Muzio et al., Cell 1996, Medema et al., EMBO J 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: FASLG/FAS (trimer)/FADD/FADD/CASP8/CASP8 complex (FAS-FASLG-FADD-CASP8) → c-FLIP p12 (CFLAR) (modification, collaborate) Yeh et al., Immunity 2000, Krueger et al., J Biol Chem 2001, Algeciras-Schimnich et al., Mol Cell Biol 2002, Chang et al., EMBO J 2002, Geserick et al., J Cell Biol 2009, Muzio et al., Cell 1996, Medema et al., EMBO J 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: c-FLIP (CFLAR) → FASLG/FAS (trimer)/FADD/FADD complex (FAS-FASLG-FADD) (modification, collaborate)
  Yeh et al., Immunity 2000, Krueger et al., J Biol Chem 2001, Algeciras-Schimnich et al., Mol Cell Biol 2002, Chang et al., EMBO J 2002, Geserick et al., J Cell Biol 2009, Muzio et al., Cell 1996, Medema et al., EMBO J 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: c-FLIP (CFLAR) → FASLG/FAS (trimer)/FADD/FADD/CFLIP complex (FAS-FASLG-FADD-CFLAR) (modification, collaborate)
  Yeh et al., Immunity 2000, Krueger et al., J Biol Chem 2001, Algeciras-Schimnich et al., Mol Cell Biol 2002, Chang et al., EMBO J 2002, Geserick et al., J Cell Biol 2009, Muzio et al., Cell 1996, Medema et al., EMBO J 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: c-FLIP (CFLAR) → FASLG/FAS (trimer)/FADD/FADD/CASP8 p43/c-FLIP p43 complex (FAS-FASLG-FADD-CASP8-CFLAR) (modification, collaborate)
  Yeh et al., Immunity 2000, Krueger et al., J Biol Chem 2001, Algeciras-Schimnich et al., Mol Cell Biol 2002, Chang et al., EMBO J 2002, Geserick et al., J Cell Biol 2009, Muzio et al., Cell 1996, Medema et al., EMBO J 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: Caspase 8 p10 (CASP8) → FASLG/FAS (trimer)/FADD/FADD/CFLIP complex (FAS-FASLG-FADD-CFLAR) (modification, collaborate)
  Yeh et al., Immunity 2000, Krueger et al., J Biol Chem 2001, Algeciras-Schimnich et al., Mol Cell Biol 2002, Chang et al., EMBO J 2002, Geserick et al., J Cell Biol 2009, Muzio et al., Cell 1996, Medema et al., EMBO J 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: Caspase 8 p10 (CASP8) → FASLG/FAS (trimer)/FADD/FADD/CASP8 p43/c-FLIP p43 complex (FAS-FASLG-FADD-CASP8-CFLAR) (modification, collaborate)
  Yeh et al., Immunity 2000, Krueger et al., J Biol Chem 2001, Algeciras-Schimnich et al., Mol Cell Biol 2002, Chang et al., EMBO J 2002, Geserick et al., J Cell Biol 2009, Muzio et al., Cell 1996, Medema et al., EMBO J 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: FASLG/FAS (trimer)/FADD/FADD complex (FAS-FASLG-FADD) → FASLG/FAS (trimer)/FADD/FADD/CFLIP complex (FAS-FASLG-FADD-CFLAR) (modification, collaborate)
  Yeh et al., Immunity 2000, Krueger et al., J Biol Chem 2001, Algeciras-Schimnich et al., Mol Cell Biol 2002, Chang et al., EMBO J 2002, Geserick et al., J Cell Biol 2009, Muzio et al., Cell 1996, Medema et al., EMBO J 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: FASLG/FAS (trimer)/FADD/FADD complex (FAS-FASLG-FADD) → FASLG/FAS (trimer)/FADD/FADD/CASP8 p43/c-FLIP p43 complex (FAS-FASLG-FADD-CASP8-CFLAR) (modification, collaborate)
  Yeh et al., Immunity 2000, Krueger et al., J Biol Chem 2001, Algeciras-Schimnich et al., Mol Cell Biol 2002, Chang et al., EMBO J 2002, Geserick et al., J Cell Biol 2009, Muzio et al., Cell 1996, Medema et al., EMBO J 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: FASLG/FAS (trimer)/FADD/FADD complex (FAS-FASLG-FADD) → c-FLIP p12 (CFLAR) (modification, collaborate) Yeh et al., Immunity 2000, Krueger et al., J Biol Chem 2001, Algeciras-Schimnich et al., Mol Cell Biol 2002, Chang et al., EMBO J 2002, Geserick et al., J Cell Biol 2009, Muzio et al., Cell 1996, Medema et al., EMBO J 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: FASLG/FAS (trimer)/FADD/FADD/CFLIP complex (FAS-FASLG-FADD-CFLAR) → FASLG/FAS (trimer)/FADD/FADD/CASP8 p43/c-FLIP p43 complex (FAS-FASLG-FADD-CASP8-CFLAR) (modification, collaborate)
  Yeh et al., Immunity 2000, Krueger et al., J Biol Chem 2001, Algeciras-Schimnich et al., Mol Cell Biol 2002, Chang et al., EMBO J 2002, Geserick et al., J Cell Biol 2009, Muzio et al., Cell 1996, Medema et al., EMBO J 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: FASLG/FAS (trimer)/FADD/FADD/CFLIP complex (FAS-FASLG-FADD-CFLAR) → c-FLIP p12 (CFLAR) (modification, collaborate) Yeh et al., Immunity 2000, Krueger et al., J Biol Chem 2001, Algeciras-Schimnich et al., Mol Cell Biol 2002, Chang et al., EMBO J 2002, Geserick et al., J Cell Biol 2009, Muzio et al., Cell 1996, Medema et al., EMBO J 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: FASLG/FAS (trimer)/FADD/FADD/CASP8 p43/c-FLIP p43 complex (FAS-FASLG-FADD-CASP8-CFLAR) → c-FLIP p12 (CFLAR) (modification, collaborate) Yeh et al., Immunity 2000, Krueger et al., J Biol Chem 2001, Algeciras-Schimnich et al., Mol Cell Biol 2002, Chang et al., EMBO J 2002, Geserick et al., J Cell Biol 2009, Muzio et al., Cell 1996, Medema et al., EMBO J 1997
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database FAS (CD95) signaling pathway: c-FLIPS (CFLAR) → FASLG/FAS (trimer)/FADD/FADD/CASP8/c-FLIPS complex (FAS-FASLG-FADD-CASP8-CFLAR) (modification, collaborate)
  Krueger et al., J Biol Chem 2001, Chang et al., EMBO J 2002
  Evidence: assay
• NCI Pathway Database FAS (CD95) signaling pathway: c-FLIPS (CFLAR) → FASLG/FAS (trimer)/FADD/FADD complex (FAS-FASLG-FADD) (modification, collaborate)
  Krueger et al., J Biol Chem 2001, Chang et al., EMBO J 2002
  Evidence: assay
• NCI Pathway Database FAS (CD95) signaling pathway: Caspase 8 (CASP8) → FASLG/FAS (trimer)/FADD/FADD/CASP8/c-FLIPS complex (FAS-FASLG-FADD-CASP8-CFLAR) (modification, collaborate)
  Krueger et al., J Biol Chem 2001, Chang et al., EMBO J 2002
  Evidence: assay
• NCI Pathway Database FAS (CD95) signaling pathway: FASLG/FAS (trimer)/FADD/FADD/CASP8/c-FLIPS complex (FAS-FASLG-FADD-CASP8-CFLAR) → FASLG/FAS (trimer)/FADD/FADD complex (FAS-FASLG-FADD) (modification, collaborate)
  Krueger et al., J Biol Chem 2001, Chang et al., EMBO J 2002
  Evidence: assay
• NCI Pathway Database HIV-1 Nef: Negative effector of Fas and TNF-alpha: c-FLIP (CFLAR) → FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG complex (FASLG-CASP8-MAP3K5-FAS-DAXX-FADD) (modification, inhibits)
  Medema et al., EMBO J 1997
• Reactome Reaction: FAS → CFLAR (indirect_complex) Siegmund et al., J Biol Chem 2001, Micheau et al., Mol Cell Biol 2001*, Micheau et al., J Biol Chem 2002*, Kreuz et al., J Cell Biol 2004, Kim et al., Journal of molecular signaling 2008*, Fricker et al., J Cell Biol 2010*, Pop et al., Biochem J 2011*, Scaffidi et al., J Biol Chem 1999
• Reactome Reaction: FAS → CFLAR (reaction) Siegmund et al., J Biol Chem 2001, Micheau et al., Mol Cell Biol 2001*, Micheau et al., J Biol Chem 2002*, Kreuz et al., J Cell Biol 2004, Kim et al., Journal of molecular signaling 2008*, Fricker et al., J Cell Biol 2010*, Pop et al., Biochem J 2011*, Scaffidi et al., J Biol Chem 1999

Protein-Protein interactions - manually collected from original source literature:

Studies that report less than 10 interactions are marked with *

• IRef Biogrid Interaction: FAS — CFLAR (physical association, affinity chromatography technology) Shu et al., Immunity 1997*
• IRef Biogrid Interaction: FAS — CFLAR (physical association, affinity chromatography technology) MacFarlane et al., J Biol Chem 1997
• MIPS CORUM Death induced signaling complex DISC (FAS, FADD, CASP8, CFLAR), membrane-associated, CD95L induced: Death induced signaling complex DISC (FAS, FADD, CASP8, CFLAR), membrane-associated, CD95L induced complex (CASP8-CFLAR-FADD-FAS) Lavrik et al., J Biol Chem 2008
• IRef Hprd Interaction: Complex of 17 proteins MacFarlane et al., J Biol Chem 1997
• IRef Intact Interaction: Complex of FADD-FAS-CFLAR-CASP8 (association, anti bait coimmunoprecipitation) Tao et al., Blood 2011
• IRef Intact Interaction: Complex of FAS-CFLAR-CFLAR-FAS (association, anti bait coimmunoprecipitation) Tao et al., Blood 2011
• IRef Intact Interaction: Complex of CFLAR-FAS-CASP8-CFLAR-FAS-CASP8 (association, anti bait coimmunoprecipitation) Shatnyeva et al., PloS one 2011*
• IRef Intact Interaction: Complex of 17 proteins (association, anti bait coimmunoprecipitation) Tao et al., Blood 2011

Text-mined interactions from Literome

Hyer et al., Cancer Biol Ther 2002 (Prostatic Neoplasms) : These data suggest that c-FLIP may play a critical role in regulating Fas mediated apoptosis in prostate cancer cells and that modulation of c-FLIP may enhance Fas signaling based therapies
Gilbert et al., Mol Cell Biol 2004 (MAP Kinase Signaling System) : c-Flip, along with Raf-1, is part of a K8/K18 immunoisolated complex from wild-type hepatocytes, and Fas stimulation leads to further c-Flip and Raf-1 recruitment in the complex
Park et al., Mol Cancer Ther 2008 (Carcinoma, Hepatocellular...) : Mitogen activated protein kinase kinase 1/2 inhibitors and 17-allylamino-17-demethoxygeldanamycin synergize to kill human gastrointestinal tumor cells in vitro via suppression of c-FLIP-s levels and activation of CD95
García et al., Rheumatology (Oxford) 2009 (Arthritis, Rheumatoid) : Inhibition of PI3K/Akt pathway did not modify the difference between PARP-1-competent or -deficient FLS in Fas mediated apoptosis or c-FLIP-S expression
Walker et al., Mol Pharmacol 2009 (Colonic Neoplasms) : In SW480 cells, sorafenib + vorinostat increased CD95 plasma membrane levels and promoted death inducing signal complex ( DISC ) formation, and drug toxicity was blocked by knockdown of CD95 or overexpression of cellular FLICE-like inhibitory protein ( c-FLIP-s )
Kavuri et al., J Biol Chem 2011 : cFLIP mediated inhibition of CD95 and TRAIL DR could be of crucial importance during keratinocyte skin carcinogenesis and for the activation of innate and/or adaptive immune responses triggered by DR activation in the skin