Debcl, a proapoptotic Bcl-2 homologue, is a component of the Drosophila melanogaster cell death machinery

Bcl-2 family of proteins are key regulators of apoptosis. Both proapoptotic and antiapoptotic members of this family are found in mammalian cells, but no such proteins have been described in insects. Here, we report the ident ification and characterization of Debcl, the first Bcl-2 homologue in Droso phila melanogaster. Structurally, Debcl is similar to Bar-like proapoptotic Bcl-2 family members. Ectopic expression of Debcl in cultured cells and in transgenic flies causes apoptosis, which is inhibited by coexpression of t he baculovirus caspase inhibitor P35, indicating that Debcl is a proapoptot ic protein that functions in a caspase-dependent manner, debcl expression c orrelates with developmental cell death in specific Drosophila tissues. We also show that debcl genetically interacts with diap1 and dark, and that de bcl-mediated apoptosis is not affected by gene dosage of rpr, hid, and grim . Biochemically, Debcl can interact with several mammalian and viral prosur vival Bcl-2 family members, but not with the proapoptotic members, suggesti ng that it may regulate apoptosis by antagonizing prosurvival Bcl-2 protein s. RNA interference studies indicate that Debcl is required for development al apoptosis in Drosophila embryos. These results suggest that the main com ponents of the mammalian apoptosis machinery are conserved in insects.