The Drosophila caspase DRONC is regulated by DIAP1

We have isolated the recently identified Drosophila caspase DRONC through i ts interaction with the effector caspase drICE, Ectopic expression of DRONC induces cell death in Schizosaccharomyces pombe, mammalian fibroblasts and the developing Drosophila eye. The caspase inhibitor p35 fails to rescue D RONC-induced cell death in vivo and is not cleaved by DRONC in vitro, makin g DRONC the first identified p35-resistant caspase, The DRONC pro-domain in teracts with Drosphila inhibitor of apoptosis protein 1 (DIAP1), and co-exp ression of DIAP1 in the developing Drosophila eye completely reverts the ey e ablation phenotype induced by pro-DRONC expression, In contrast, DIAP1 fa ils to rescue eye ablation induced by DRONC lacking the pro-domain, indicat ing that interaction of DIAP1 with the pro-domain of DRONC is required for suppression of DRONC-mediated cell death. Heterozygosity at the diap1 locus enhances the pro-DRONC eye phenotype, consistent with a role for endogenou s DIAP1 in suppression of DRONC activation, Both heterozygosity at the dron e locus and expression of dominant-negative DRONC mutants suppress the eye phenotype caused by reaper (RPR) and head involution defective (HID), consi stent with the idea that DRONC functions in the RPR and HID pathway.