Activation of distinct caspase-like proteases by Fas and reaper in Drosophila cells.
The cytoplasmic region of Fas, a mammalian death factor receptor, shares a limited homology with reaper, an apoptosis-inducing protein in Drosophila. Expression of either the Fas cytoplasmic region (FasC) or of reaper in Drosophila cells caused cell death. The death process induced by FasC or reaper was inhibited by crmA or p35, suggesting that its death process is mediated by caspase-like proteases. Both Ac-YVAD aldehyde and Ac-DEVD aldehyde, specific inhibitors of caspase 1- and caspase 3-like proteases, respectively, inhibited the FasC-induced death of Drosophila cells. However, the cell death induced by reaper was inhibited by Ac-DEVD aldehyde, but not by Ac-YVAD aldehyde. A caspase 1-like protease activity that preferentially recognizes the YVAD sequence gradually increased in the cytosolic fraction of the FasC-activated cells, whereas the caspase 3-like protease activity recognizing the DEVD sequence was observed in the reaper-activated cells. Partial purification and biochemical characterization of the proteases indicated that there are at least three distinct caspase-like proteases in Drosophila cells, which are differentially activated by FasC and reaper. The conservation of the Fas-death signaling pathway in Drosophila cells, which is distinct from that for reaper, may indicate that cell death in Drosophila is controlled not only by the reaper suicide gene, but also by a Fas-like killer gene.
Kondo
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T
Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565, Japan.
Yokokura
T
T
Nagata
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S
D000818:Animals; D017209:Apoptosis; D020170:Caspase 1; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004330:Drosophila / Q000166:cytology / Q000378:metabolism*; D029721:Drosophila Proteins; D004789:Enzyme Activation; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
D015853:Cysteine Proteinase Inhibitors; D029721:Drosophila Proteins; D010446:Peptide Fragments; D010455:Peptides; D019014:fas Receptor; C086973:rpr protein, Drosophila; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D020170:Caspase 1