Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor

EMBO J. 1995 Nov 15;14(22):5579-88.

Abstract

APO-1 (Fas/CD95), a member of the tumor necrosis factor receptor superfamily, induces apoptosis upon receptor oligomerization. In a search to identify intracellular signaling molecules coupling to oligomerized APO-1, several cytotoxicity-dependent APO-1-associated proteins (CAP) were immunoprecipitated from the apoptosis-sensitive human leukemic T cell line HUT78 and the lymphoblastoid B cell line SKW6.4. CAP1-3 (27-29 kDa) and CAP4 (55 kDa), instantly detectable after the crosslinking of APO-1, were associated only with aggregated (the signaling form of APO-1) and not with monomeric APO-1. CAP1 and CAP2 were identified as serine phosphorylated MORT1/FADD. The association of CAP1-4 with APO-1 was not observed with C-terminally truncated non-signaling APO-1. In addition, CAP1 and CAP2 did not associate with an APO-1 cytoplasmic tail carrying the lprcg amino acid replacement. Moreover, no APO-1-CAP association was found in the APO-1+, anti-APO-1-resistant pre-B cell line Boe. Our data suggest that in vivo CAP1-4 are the APO-1 apoptosis-transducing molecules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Apoptosis / physiology*
  • Base Sequence
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Caspase 8
  • Caspase 9
  • Caspases*
  • Cell Line
  • Cross-Linking Reagents
  • Cysteine Endopeptidases / metabolism
  • DNA Primers
  • Fas-Associated Death Domain Protein
  • Humans
  • Lymphocytes / physiology
  • Molecular Sequence Data
  • Phosphorylation
  • Tumor Cells, Cultured
  • fas Receptor / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Cross-Linking Reagents
  • DNA Primers
  • FADD protein, human
  • Fas-Associated Death Domain Protein
  • fas Receptor
  • CASP8 protein, human
  • CASP9 protein, human
  • Caspase 8
  • Caspase 9
  • Caspases
  • Cysteine Endopeptidases