A MOUSE FAS-ASSOCIATED PROTEIN WITH HOMOLOGY TO THE HUMAN MORT1 FADD PROTEIN IS ESSENTIAL FOR FAS-INDUCED APOPTOSIS/

The Fas cell surface receptor belongs to the tumor necrosis factor rec eptor family and can initiate apoptosis in a variety of cell types. Us ing the Fas cytoplasmic domain as bait in a yeast two-hybrid screening , we isolated a mouse cDNA encoding a 205-amino-acid protein. Its pred icted protein sequence shows 68% identity and 80% similarity with the sequence of recently described human Mort1/FADD. This protein, most li kely the mouse homolog of human FADD, associates with Fas in vivo only upon the induction of cell death. A fraction of this protein is highl y phosphorylated at serine/threonine residues, with both phosphorylate d and unphosphorylated forms being capable of binding to Fas. Stable e xpression of a truncated form of the Mort1/FADD protein protects cells from Fas-mediated apoptosis by interfering with the wild-type protein -Pas interaction. Thus, mouse Mort1/FADD is an essential downstream co mponent that mediates Fas-induced apoptosis.