Casper is a FADD- and caspase-related inducer of apoptosis

Caspases are cysteine proteases that play a central role in Apoptosis. Caspase-8 may be the first Enzyme of the proteolytic cascade activated by the Fas ligand and tumor necrosis factor (TNF). Caspase-8 is recruited to Fas and TNF receptor-1 (TNF-R1) through interaction of its prodomain with the death effector domain (DED) of the receptor-associating FADD. Here we describe a novel 55 kDa protein, Casper, that has sequence similarity to Caspase-8 throughout its length. However, Casper is not a Caspase since it lacks several conserved Amino acids found in all caspases. Casper interacts with FADD, Caspase-8, Caspase-3, TRAF1, and TRAF2 through distinct domains. When overexpressed in mammalian cells, Casper potently induces Apoptosis. A C-terminal deletion mutant of Casper inhibits TNF- and Fas-induced cell death, suggesting that Casper is involved in these apoptotic pathways.