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The Drosophila Caspase DRONC Cleaves following Glutamate or Aspartate and Is Regulated by DIAP1, HID, and GRIM

Hawkins, Christine J. and Yoo, Soon Ji and Peterson, Erin P. and Wang, Susan L. and Vernooy, Stephanie Y. and Hay, Bruce A. (2000) The Drosophila Caspase DRONC Cleaves following Glutamate or Aspartate and Is Regulated by DIAP1, HID, and GRIM. Journal of Biological Chemistry, 275 (35). pp. 27084-27093. ISSN 0021-9258. doi:10.1074/jbc.M000869200.

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The caspase family of cysteine proteases plays important roles in bringing about apoptotic cell death. All caspases studied to date cleave substrates COOH-terminal to an aspartate. Here we show that the Drosophila caspase DRONC cleaves COOH-terminal to glutamate as well as aspartate. DRONC autoprocesses itself following a glutamate residue, but processes a second caspase, drICE, following an aspartate. DRONC prefers tetrapeptide substrates in which aliphatic amino acids are present at the P2 position, and the P1 residue can be either aspartate or glutamate. Expression of a dominant negative form of DRONC blocks cell death induced by the Drosophila cell death activators reaper, hid, and grim, and DRONC overexpression in flies promotes cell death. Furthermore, the Drosophila cell death inhibitor DIAP1 inhibits DRONC activity in yeast, and DIAP1's ability to inhibit DRONC-dependent yeast cell death is suppressed by HID and GRIM. These observations suggest that DRONC acts to promote cell death. However, DRONC activity is not suppressed by the caspase inhibitor and cell death suppressor baculovirus p35. We discuss possible models for DRONC function as a cell death inhibitor.

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Additional Information:© 2000 by The American Society for Biochemistry and Molecular Biology, Inc. Received for publication, January 31, 2000, and in revised form, May 15, 2000. Originally published In Press as doi:10.1074/jbc.M000869200 on May 23, 2000 We thank Becky Green-Maruoquin for sectioning Drosophila eyes and Gary M. Hathaway for microsequencing. This work was supported in part by grants from the Burroughs Wellcome Fund (New Investigator awards in the Pharmacological Sciences), the Ellison Medical Foundation, and National Institutes of Health Grant GM057422-01 (to B. A. H.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. [C.J.H. and S.J.Y.] [c]ontributed equally to the results of this work. [C.J.H. was] [s]upported by a Human Frontiers postdoctoral fellowship. [S.J.Y. was] [s]upported by a Jane Coffin Child postdoctoral fellowship. [B.A.H. is a] Searle Scholar.
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Burroughs Wellcome FundUNSPECIFIED
Ellison Medical FoundationUNSPECIFIED
Human Frontier Science ProgramUNSPECIFIED
Jane Coffin Childs Memorial Fund for Medical ResearchUNSPECIFIED
Searle Scholars ProgramUNSPECIFIED
Issue or Number:35
Record Number:CaltechAUTHORS:HAWjbc00
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:4212
Deposited By: Archive Administrator
Deposited On:08 Aug 2006
Last Modified:08 Nov 2021 20:15

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