RRC ID 1780
Author Leulier F, Ribeiro PS, Palmer E, Tenev T, Takahashi K, Robertson D, Zachariou A, Pichaud F, Ueda R, Meier P.
Title Systematic in vivo RNAi analysis of putative components of the Drosophila cell death machinery.
Journal Cell Death Differ.
Abstract Despite the identification of numerous key players of the cell death machinery, little is known about their physiological role. Using RNA interference (RNAi) in vivo, we have studied the requirement of all Drosophila caspases and caspase-adaptors in different paradigms of apoptosis. Of the seven caspases, Dronc, drICE, Strica and Decay are rate limiting for apoptosis. Surprisingly, Hid-mediated apoptosis requires a broader range of caspases than apoptosis initiated by loss of the caspase inhibitor DIAP1, suggesting that Hid causes apoptosis not only by antagonizing DIAP1 but also by activating DIAP1-independent caspase cascades. While Hid killing requires Strica, Decay, Dronc/Dark and drICE, apoptosis triggered by DIAP1 depletion merely relied upon Dronc/Dark and drICE. Furthermore, we found that overexpression of DIAP2 can rescue diap1-RNAi-mediated apoptosis, suggesting that DIAP2 regulates caspases directly. Consistently, we show that DIAP2 binds active drICE. Since DIAP2 associates with Hid, we propose a model whereby Hid co-ordinately targets both DIAP1 and DIAP2 to unleash drICE.
Volume 13(10)
Pages 1663-74
Published 2006-10
DOI 10.1038/sj.cdd.4401868
PII 4401868
PMID 16485033
MeSH Animals Animals, Genetically Modified Apoptosis / genetics Apoptosis / physiology* Caspase Inhibitors Caspases / genetics Caspases / physiology* Drosophila / cytology* Drosophila / enzymology* Drosophila / genetics Drosophila Proteins / genetics Drosophila Proteins / physiology Eye / cytology Eye / enzymology Eye / growth & development Genes, Insect Inhibitor of Apoptosis Proteins / genetics Inhibitor of Apoptosis Proteins / physiology Models, Biological Phenotype RNA Interference Signal Transduction
IF 8.0
Times Cited 51
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
Resource
Drosophila 8091R-1 8091R-2 7788R-1 7788R-2 5370R-1 5370R-2 7486R-1 7486R-2 7863R-2 7863R-3 18188R-1 18188R-2 14902R-2 14902R-3 12297R-1 12297R-2 GFP-IR-1 12284R-2