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

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.

JNK activation is not required for Fas-mediated apoptosis

“…FADD is recruited to the cytoplasmic tail of Fas upon triggering (Kischkel et al, 1995). Over-expression of a truncated, dominant interfering form of FADD prevents Fas stimulation of apoptosis by blocking FADD recruitment .…”

“…Fas and TNFR1 share a region of homology in the cytoplasmic tail, the death domain, which is critical for signalling apoptosis (Itoh et al, 1991;Tartaglia et al, 1993). The death domain recruits FADD upon Fas activation (Kischkel et al, 1995), this then recruits and activates caspase 8 (Muzio et al, 1996;Boldin et al, 1996). Other caspases, including 1 and 3, are subsequently activated (Enari et al, 1996) and caspase activation is necessary for Fas-mediated apoptosis (Tewari and Dixit, 1995).…”

Dexamethasone protects primary cultured hepatocytes from death receptor-mediated apoptosis by upregulation of cFLIP

“…47 In brief, hepatocytes were stimulated with 2 mg/ml biotinylated Jo2 anti-Fas-antibody plus 5 mg/ml strepavidin (Pierce) for 30 min at 371C. Cells were gently sonicated (5 s bursts, 5 W; Vibracell, Bioblock Scientific in ice-cold buffer A containing 25 mM HEPES, 150 mM NaCl, 1 mM EGTA, 1 mg/ml leupeptin, 1 mg/ml pepstatin, 2 mg/ml chymostatin, and 5 mg/ml a2 macroglobin).…”

The influence of α1-antagonist on the expression pattern of TNF receptor family in primary culture of prostate epithelial cells from BPH patients

“…Two signaling pathways (type I and II) have been identified. [16][17][18][19] TNFR-1 and TNFR-2 have significant homology in their extracellular domains; however, their cytoplasmic domains are different.…”