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Cleavage of the apoptosis inhibitor DIAP1 by the apical caspase DRONC in both normal and apoptotic drosophila cells

Muro, Israel and Means, John C. and Clem, Rollie J. (2005) Cleavage of the apoptosis inhibitor DIAP1 by the apical caspase DRONC in both normal and apoptotic drosophila cells. Journal of Biological Chemistry, 280 (19). pp. 18683-18688. ISSN 0021-9258. doi:10.1074/jbc.M501206200.

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In Drosophila S2 cells, the apical caspase DRONC undergoes a low level of spontaneous autoprocessing. Unintended apoptosis is prevented by the inhibitor of apoptosis DIAP1, which targets the processed form of DRONC for degradation through its E3 ubiquitin protein ligase activity. Recent reports have demonstrated that shortly after the initiation of apoptosis in S2 cells, DIAP1 is cleaved following aspartate residue Asp-20 by the effector caspase DrICE. Here we report a novel caspase-mediated cleavage of DIAP1 in S2 cells. In both living and dying S2 cells, DIAP1 is cleaved by DRONC after glutamate residue Glu-205, located between the first and second BIR domains. The mutation of Glu-205 prevented the interaction of DIAP1 and processed DRONC but had no effect on the interaction with full-length DRONC. The mutation of Glu-205 also had a negative effect on the ability of overexpressed DIAP1 to prevent apoptosis stimulated by the proapoptotic protein Reaper or by UV light. These results expand our knowledge of the events that occur in the Drosophila apoptosome prior to and after receiving an apoptotic signal.

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Additional Information:© 2005 The American Society for Biochemistry and Molecular Biology, Inc. Received for publication, February 1, 2005, and in revised form, March 16, 2005. Published, JBC Papers in Press, March 17, 2005. We thank Bruce Hay (California Institute of Technology) for providing reagents. This work was supported by Grant R29 CA78602 from NCI, National Institutes of Health, Grant P20 RR107686 from the National Center for Research Resources (NCRR), Grant P20 RR16475 from the BRIN Program of the NCRR, and by the Kansas Agricultural Experiment Station. This is contribution number 05-24-J from the Kansas Agricultural Experiment Station. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Funding AgencyGrant Number
NIHR29 CA78602
NIHP20 RR107686
NIHP20 RR16475
Kansas Agricultural Experiment StationUNSPECIFIED
Issue or Number:19
Record Number:CaltechAUTHORS:MURjbc05
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:3751
Deposited By: Lindsay Cleary
Deposited On:10 Jul 2006
Last Modified:08 Nov 2021 20:12

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