A NOVEL PROTEIN THAT INTERACTS WITH THE DEATH DOMAIN OF FAS APO1 CONTAINS A SEQUENCE MOTIF RELATED TO THE DEATH DOMAIN/

Signaling for cell death by Fas/APO1 occurs via a distinct region in i ts intracellular domain. This region contains a conserved sequence mot if, the death domain motif, that is also found in the intracellular do mains of p55 tumor necrosis factor receptor and the low affinity nerve growth factor receptor, as well as in the regulatory domain of the an kyrins. A novel protein that specifically binds to the death domain of Fas/APO1 but not to Fas/APO1 molecules with a loss of function point mutation occurring in lpr(cg) mice was cloned by a two-hybrid screen o f a HeLa cells' cDNA library. The cloned protein itself contains a dea th domain motif, and this region binds to the death domain of Fas/APO1 , while the region upstream to the death domain prompts self-associati on of the protein. Induced expression of the protein results in ligand -independent triggering of cytotoxicity, suggesting that it is involve d in cell death induction by Fas/APO1.