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PMID: 10675328 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 19 ·No. 4 ·2000-02-15 ·Pages 589-97

Goyal L, McCall K, Agapite J, Hartwieg E, Steller H

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.

MeSH Terms
Alleles Animals Apoptosis/genetics,physiology Drosophila/cytology,genetics,metabolism Drosophila Proteins Eye/anatomy & histology Genes, Insect Inhibitor of Apoptosis Proteins Insect Proteins/antagonists & inhibitors,genetics,physiology Microscopy, Electron, Scanning Models, Biological Mutation Neuropeptides/genetics Peptides/genetics Phenotype
Chemicals
DIAP1 protein, Drosophila Drosophila Proteins HID protein, Drosophila Inhibitor of Apoptosis Proteins Insect Proteins Neuropeptides Peptides grim protein, Drosophila rpr protein, Drosophila
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Goyal L
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Departments of Biology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
McCall K
Agapite J
Hartwieg E
Steller H
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/19.4.589
Published
2000-02-15
Pages
589-97
Language
English
Region
England
NLM ID
8208664
PMCID
PMC305597
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/19.4.589 PMC Full Text View journal details
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