INHIBITION OF FAS DEATH SIGNALS BY FLIPS

The death receptor Fas is a member of the tumor necrosis factor recept or family; upon interaction with its ligand it efficiently activates c aspases and-induces apoptosis. Despite abundant Fas surface expression , however, Fas death-signals are frequently interrupted. Many viruses express antiapoptotic proteins, including caspase inhibitors, Bcl-2 ho mologues and death-effector-domain-containing proteins that are termed FLIPs (FLICE [Fas-associated death-domain-like IL-1 beta-converting e nzyme]-inhibitory proteins). Cellular homologues of these inhibitors h ave been identified. Cellular FLIPs structurally resemble caspase-8 ex cept that they lack proteolytic activity. FLIPs are highly expressed i n tumor cells, T lymphocytes and healthy, but not injured, myocytes; t his suggests a critical role of FLIPs as endogenous modulators of apop tosis.