Induction of apoptosis by Drosophila reaper, hid and grim through inhibition of IAP function

Induction of apoptosis by Drosophila reaper, hid and grim through inhibition of IAP function Induction of apoptosis in Drosophila requires the activity of three closely linked genes, reaper, hid and grim. Here we show that the proteins encoded by reaper, hid and grim activate cell death by inhibiting the anti‐apoptotic activity of the Drosophila IAP1 (diap1) protein. In a genetic modifier screen, both loss‐of‐function and gain‐of‐function alleles in the endogenous diap1 gene were obtained, and the mutant proteins were functionally and biochemically characterized. Gain‐of‐function mutations in diap1 strongly suppressed reaper‐, hid‐ and grim‐induced apoptosis. Sequence analysis of these alleles revealed that they were caused by single amino acid changes in the baculovirus IAP repeat domains of diap1, a domain implicated in binding REAPER, HID and GRIM. Significantly, the corresponding mutant DIAP1 proteins displayed greatly reduced binding of REAPER, HID and GRIM, indicating that REAPER, HID and GRIM kill by forming a complex with DIAP1. These data provide strong in vivo evidence for a previously published model of cell death regulation in Drosophila. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The EMBO Journal Wiley

Induction of apoptosis by Drosophila reaper, hid and grim through inhibition of IAP function

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Publisher
Wiley
Copyright
Copyright © 2013 Wiley Periodicals, Inc
ISSN
0261-4189
eISSN
1460-2075
DOI
10.1093/emboj/19.4.589
Publisher site
See Article on Publisher Site

Abstract

Induction of apoptosis in Drosophila requires the activity of three closely linked genes, reaper, hid and grim. Here we show that the proteins encoded by reaper, hid and grim activate cell death by inhibiting the anti‐apoptotic activity of the Drosophila IAP1 (diap1) protein. In a genetic modifier screen, both loss‐of‐function and gain‐of‐function alleles in the endogenous diap1 gene were obtained, and the mutant proteins were functionally and biochemically characterized. Gain‐of‐function mutations in diap1 strongly suppressed reaper‐, hid‐ and grim‐induced apoptosis. Sequence analysis of these alleles revealed that they were caused by single amino acid changes in the baculovirus IAP repeat domains of diap1, a domain implicated in binding REAPER, HID and GRIM. Significantly, the corresponding mutant DIAP1 proteins displayed greatly reduced binding of REAPER, HID and GRIM, indicating that REAPER, HID and GRIM kill by forming a complex with DIAP1. These data provide strong in vivo evidence for a previously published model of cell death regulation in Drosophila.

Journal

The EMBO JournalWiley

Published: Mar 15, 2001

Keywords: ; ; ;

References

  • IAPs block apoptotic events induced by caspase‐8 and cytochrome c by direct inhibition of distinct caspases
    Deveraux, QL; Roy, N; Stennicke, HR; van Arsdale, T; Zhou, Q; Srinivasula, SM; Alnemri, ES; Salvesen, GS; Reed, J
  • DRONC, an ecdysone‐inducible Drosophila caspase
    Dorstyn, L; Colussi, PA; Quinn, LM; Richardson, H; Kumar, S
  • Reaper‐induced apoptosis in a vertebrate system
    Evans, EK; Kuwana, T; Strum, SL; Smith, JJ; Newmeyer, DD; Kornbluth, S
  • Identification of a Drosophila melanogaster ICE/CED‐3‐related protease, drICE
    Fraser, AG; Evan, GI
  • Apoptosis induced by Drosophila reaper and grim in a human system. Attenuation by inhibitor of apoptosis proteins (cIAP)
    McCarthy, JV; Dixit, VM
  • The Drosophila caspase DRONC is regulated by DIAP1
    Meier, P; Silke, J; Leevers, SJ; Evan, GI
  • Genetic control of programmed cell death in Drosophila
    White, K; Grether, ME; Abrams, JM; Young, L; Farrell, K; Steller, H

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