The Drosophila Caspase Inhibitor DIAP1 Is Essential for Cell Survival and Is Negatively Regulated by HID
Abstract
Drosophila Reaper (RPR), Head Involution Defective (HID), and GRIM induce caspase-dependent cell death and physically interact with the cell death inhibitor DIAP1. Here we show that HID blocks DIAP1's ability to inhibit caspase activity and provide evidence suggesting that RPR and GRIM can act similarly. Based on these results, we propose that RPR, HID, and GRIM promote apoptosis by disrupting productive IAP–caspase interactions and that DIAP1 is required to block apoptosis-inducing caspase activity. Supporting this hypothesis, we show that elimination of DIAP1 function results in global early embryonic cell death and a large increase in DIAP1-inhibitable caspase activity and that DIAP1 is still required for cell survival when expression of rpr, hid, and grim is eliminated.
Additional Information
© 1999 Cell Press. Received 28 May 1999, Revised 13 July 1999. We thank R. Deshaies and members of his lab for advice with protein binding and yeast experiments and H. Schwarz and J. Berger (MPI Tübingen, Germany) for the use of their SEM. We also thank R. Deshaies, P. Sternberg, and M. Guo for comments on the manuscript. H.-A. J. M. thanks E. Wieschaus for discussions. C. J. H. is supported by a Human Frontiers postdoctoral fellowship. B. A. H. is a Searle Scholor. This work was supported by a DFG research fellowship (MU1168/1-1) to H.-A. J. M. and by grants to B. A. H. from the Gustavus and Louise Pfeiffer Research Foundation, a Burroughs Wellcome Fund New Investigator Award in the Pharmacological Sciences, the Ellison Medical Foundation, and National Institutes of Health Grant GM057422-01.Additional details
- Eprint ID
- 76000
- DOI
- 10.1016/S0092-8674(00)81974-1
- Resolver ID
- CaltechAUTHORS:20170408-144444838
- Human Frontier Science Program
- Searle Scholars Program
- MU1168/1-1
- Deutsche Forschungsgemeinschaft (DFG)
- Gustavus and Louise Pfeiffer Research Foundation
- Burroughs Wellcome Fund
- Ellison Medical Foundation
- GM057422-01
- NIH
- Created
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2017-05-04Created from EPrint's datestamp field
- Updated
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2021-11-15Created from EPrint's last_modified field