REQUIREMENT OF AN ICE-LIKE PROTEASE FOR INDUCTION OF APOPTOSIS AND CERAMIDE GENERATION BY REAPER

Genetic studies indicated that the Drosophila melanogaster protein REA PER (RPR) controls apoptosis during embryo development. Induction of R PR expression in Drosophila Schneider cells rapidly stimulated apoptos is. RPR-mediated apoptosis was blocked by N-benzyloxycarbonyl-Val-Ala- Asp-fluoromethylketone (Z-VAD-fmk) which suggests that an interleukin- 1 beta converting enzyme (ICE)-like protease is required for RPR funct ion. RPR-induced apoptosis was associated with increased ceramide prod uction that was also blocked by Z-VAD-fmk, which suggests that ceramid e generation requires an ICE-like protease as well. Thus, the intracel lular RPR protein uses cell death signaling pathways similar to those used by the vertebrate transmembrane receptors Fas (CD95) and tumor ne crosis factor receptor type 1.