Requirement of an ICE-like protease for induction of apoptosis and ceramide generation by REAPER.
Genetic studies indicated that the Drosophila melanogaster protein REAPER (RPR) controls apoptosis during embryo development. Induction of RPR expression in Drosophila Schneider cells rapidly stimulated apoptosis. 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 function. RPR-induced apoptosis was associated with increased ceramide production that was also blocked by Z-VAD-fmk, which suggests that ceramide generation requires an ICE-like protease as well. Thus, the intracellular RPR protein uses cell death signaling pathways similar to those used by the vertebrate transmembrane receptors Fas (CD95) and tumor necrosis factor receptor type 1.
Pronk
G J
GJ
Chiron Corporation, Emeryville, CA 94608, USA.
Ramer
K
K
Amiri
P
P
Williams
L T
LT
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020170:Caspase 1; D002460:Cell Line; D002518:Ceramides / Q000378:metabolism* / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D019327:Copper Sulfate; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000166:cytology* / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D015870:Gene Expression; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000502:physiology*; D011480:Protease Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D014162:Transfection
D000590:Amino Acid Chloromethyl Ketones; D002518:Ceramides; D029721:Drosophila Proteins; D010455:Peptides; D011480:Protease Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C086973:rpr protein, Drosophila; D003300:Copper; D003546:Cysteine Endopeptidases; D020170:Caspase 1; D019327:Copper Sulfate