DOOM, A PRODUCT OF THE DROSOPHILA MOD(MDG4) GENE, INDUCES APOPTOSIS AND BINDS TO BACULOVIRUS INHIBITOR-OF-APOPTOSIS PROTEINS

A family of baculovirus inhibitor-of-apoptosis (IAP) genes is present in mammals, insects, and baculoviruses, but the mechanism by which the y block apoptosis is unknown. We have identified a protein encoded by the Drosophila mod(mdg4) gene which bound to the baculovirus IAPs. Thi s protein induced rapid apoptosis in insect cells, and consequently we have named it Doom. Baculovirus IAPs and P35, an inhibitor of asparta te-specific cysteine proteases, blocked Doom-induced apoptosis. The ca rboxyl terminus encoded by the 3' exon of the doom cDNA, which disting uishes it from other mod(mdg4) cDNAs, was responsible for induction of apoptosis and engagement of the IAPs. Doom localized to the nucleus, while the IAPs localized to the cytoplasm, but when expressed together , Doom and the IAPs both localized in the nucleus. Thus, IAPs might bl ock apoptosis by interacting with and modifying the behavior of Doom-l ike proteins that reside in cellular apoptotic pathways.