SADS: A new component of Fas-DISC is the accelerator for cell death signaling and is downregulated in patients with colon carcinoma

Abstract

Fas is the death receptor, transducing cell death signaling upon stimulation by Fas ligand. During Fas-initiated cell death signaling, the formation of Fas-death inducing signaling complex (Fas-DISC) is the first step. Here we have identified a new component of Fas-DISC which we call 'small-accelerator for death signaling' (SADS). SADS cDNA encodes a 150 amino acid polypeptide (Mr = 16,700). During Fas-mediated cell death, SADS enhances the interaction of Fas-death domain-interactive factors (FADD) and procaspase-8, and deletion mutant analysis has identified FADD- and caspase-8-interactive domains in SADS. Inhibition or removal of SADS delays Fas-mediated cell death. In addition, we demonstrate the deletion or mutation of SADS in patients with colon carcinoma and that exogenous SADS expression in human colon carcinoma SW480 cells that lack SADS leads to re-acquisition of Fas-mediated cell death. Here, we propose that SADS is one of the cell death-associated factors and enhances Fas-DISC formation, especially FADD and procaspase-8 recruitment.