DREDD, A NOVEL EFFECTOR OF THE APOPTOSIS ACTIVATORS REAPER, GRIM, ANDHID IN DROSOPHILA

Caspases are widely conserved proteases considered to be essential eff ecters of apoptosis. We identified a novel Drosophila gene, dredd, whi ch shares extensive homology to all members of the caspase gene family . Cells specified for programmed death in development exhibit a striki ng accumulation of dredd RNA that requires signaling by the death acti vators REAPER, GRIM, and HID. Furthermore, directed misexpression of e ach activator was sufficient to drive ectopic accumulation of dredd RN A. Heterozygosity at the dredd locus suppressed apoptosis in transgeni c models of reaper- and grim-induced cell killing, demonstrating that levels of dredd product can modulate signaling triggered by these deat h activators. Finally, expression of REAPER, GRIM, and HID was found t o trigger processing of DREDD protein precursor through a mechanism th at is insensitive to, and upstream of, known caspase inhibitors. Taken together, these observations establish mechanistic connections betwee n activators of apoptosis and a new downstream death effector in Droso phila. (C) 1998 Academic Press.