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The Drosophila caspase DRONC is regulated by DIAP1
Author(s) -
Meier Pascal,
Silke John,
Leevers Sally J.,
Evan Gerard I.
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.4.598
Subject(s) - biology , ectopic expression , caspase , programmed cell death , microbiology and biotechnology , inhibitor of apoptosis , apoptosis , genetics , cell culture
We have isolated the recently identified Drosophila caspase DRONC through its 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 DRONC‐induced cell death in vivo and is not cleaved by DRONC in vitro , making DRONC the first identified p35‐resistant caspase. The DRONC pro‐domain interacts with Drosphila inhibitor of apoptosis protein 1 (DIAP1), and co‐expression of DIAP1 in the developing Drosophila eye completely reverts the eye ablation phenotype induced by pro‐DRONC expression. In contrast, DIAP1 fails to rescue eye ablation induced by DRONC lacking the pro‐domain, indicating 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 endogenous DIAP1 in suppression of DRONC activation. Both heterozygosity at the dronc locus and expression of dominant‐negative DRONC mutants suppress the eye phenotype caused by reaper (RPR) and head involution defective (HID), consistent with the idea that DRONC functions in the RPR and HID pathway.