Gene interactions and pathways from curated databases and text-mining
J Biol Chem 2008, PMID: 18635548

CD95 stimulation results in the formation of a novel death effector domain protein-containing complex.

Lavrik, Inna N; Mock, Thomas; Golks, Alexander; Hoffmann, Julia C; Baumann, Simone; Krammer, Peter H

Stimulation of CD95 (APO-1/Fas) by its natural ligand CD95L (APO-1L/FasL) leads to the formation of the death-inducing signaling complex. Here we report that upon CD95 stimulation in several T and B cell lines, a novel signaling complex is formed, which we term complex II. Complex II is composed of the death effector domain proteins as follows: procaspase-8a/b, three isoforms of c-FLIP (c-FLIP(L), c-FLIP(S), c-FLIP(R)), and FADD. Notably, complex II does not contain CD95. Based on our findings we suggest that CD95 signaling includes two steps. The first step involves formation of the death-inducing signaling complex at the cell membrane. The second step involves formation of the cytosolic death effector domain protein-containing complex that may play an important role in amplification of caspase activation.

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Text Mining Data

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Manually curated Databases

  • MIPS CORUM Death induced signaling complex II (FADD, CASP8, CFLAR), cytosolic, CD95L induced: Death induced signaling complex II (FADD, CASP8, CFLAR), cytosolic, CD95L induced complex (CASP8-CFLAR-FADD)
  • 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)
  • NCI Pathway Database Caspase Cascade in Apoptosis: sTNF-alpha/TNFR1A/TRADD/TRAF2/FADD complex (TNFRSF1A-TRADD-TRAF2-FADD-TNF) → Caspase 8 (CASP8) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database Caspase Cascade in Apoptosis: sTNF-alpha/TNFR1A/TRADD/TRAF2/FADD complex (TNFRSF1A-TRADD-TRAF2-FADD-TNF) → TRAIL/TRAILR2/FADD complex (TNFRSF10B-FADD-TNFSF10) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database Caspase Cascade in Apoptosis: sTNF-alpha/TNFR1A/TRADD/TRAF2/FADD complex (TNFRSF1A-TRADD-TRAF2-FADD-TNF) → FASLG/FAS (trimer)/FADD/FADD complex (FAS-FASLG-FADD) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database Caspase Cascade in Apoptosis: TRAIL/TRAILR2/FADD complex (TNFRSF10B-FADD-TNFSF10) → FASLG/FAS (trimer)/FADD/FADD complex (FAS-FASLG-FADD) (modification, activates)
    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) → clathrin heavy chain (CLTC) (translocation, collaborate)
    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) → FADD/FADD/CASP8/CASP8 complex (FADD-CASP8) (translocation, collaborate)
    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) complex (FAS-FASLG) (translocation, collaborate)
    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) → Ezrin (EZR) (translocation, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database FAS (CD95) signaling pathway: clathrin heavy chain (CLTC) → FADD/FADD/CASP8/CASP8 complex (FADD-CASP8) (translocation, activates)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database FAS (CD95) signaling pathway: clathrin heavy chain (CLTC) → FASLG/FAS (trimer) complex (FAS-FASLG) (translocation, activates)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database FAS (CD95) signaling pathway: clathrin heavy chain (CLTC) → Ezrin (EZR) (translocation, activates)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database FAS (CD95) signaling pathway: FADD/FADD/CASP8/CASP8 complex (FADD-CASP8) → FASLG/FAS (trimer) complex (FAS-FASLG) (translocation, collaborate)
    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) → Caspase 8 (tetramer)/FADD/FADD complex (CASP8-FADD) (modification, inhibits)
    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) complex (FAS-FASLG) (modification, inhibits)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database FAS (CD95) signaling pathway: Caspase 8 (tetramer)/FADD/FADD complex (CASP8-FADD) → FASLG/FAS (trimer) complex (FAS-FASLG) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
In total, 59 gene pairs are associated to this article in curated databases