CYTOTOXICITY-DEPENDENT APO-1 (FAS/CD95)-ASSOCIATED PROTEINS FORM A DEATH-INDUCING SIGNALING COMPLEX (DISC) WITH THE RECEPTOR

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 lpr(cg) amino acid replacement, Moreover, no APO-1-CAP association was found in the APO-1(+), anti-APO-1-resistant pre-B cell line Poe, Our data suggest that in vivo CAP1-4 are the APO-1 apoptosis-transducing molecules.