RIP - A NOVEL PROTEIN CONTAINING A DEATH DOMAIN THAT INTERACTS WITH FAS APO-1 (CD95) IN YEAST AND CAUSES CELL-DEATH/

Ligation of the extracellular domain of the cell surface receptor Fas/ APO-1 (CD95) elicits a characteristic programmed death response in sus ceptible cells. Using a genetic selection based on protein-protein int eraction in yeast, we have identified two gene products that associate with the intracellular domain of Pas: Pas itself, and a novel 74 kDa protein we have named RIP, for receptor interacting protein. RIP also interacts weakly with the p55 tumor necrosis factor receptor (TNFR1) i ntracellular domain, but not with a mutant version of Pas correspondin g to the murine lpr(cg) mutation. RIP contains an N-terminal region wi th homology to protein kinases and a C-terminal region containing a cy toplasmic motif (death domain) present in the Pas and TNFR1 intracellu lar domains. Transient overexpression of RIP causes transfected cells to undergo the morphological changes characteristic of apoptosis. Take n together, these properties indicate that RIP is a novel form of apop tosis-inducing protein.