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Drosophila IAP antagonists form multimeric complexes to promote cell death

Apoptosis is a specific form of cell death that is important for normal development and tissue homeostasis. Caspases are critical executioners of apoptosis, and living cells prevent their inappropriate activation through inhibitor of apoptosis proteins (IAPs). In Drosophila, caspase activation depen...

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Detalles Bibliográficos
Autores principales: Sandu, Cristinel, Ryoo, Hyung Don, Steller, Hermann
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101595/
https://www.ncbi.nlm.nih.gov/pubmed/20837774
http://dx.doi.org/10.1083/jcb.201004086
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author Sandu, Cristinel
Ryoo, Hyung Don
Steller, Hermann
author_facet Sandu, Cristinel
Ryoo, Hyung Don
Steller, Hermann
author_sort Sandu, Cristinel
collection PubMed
description Apoptosis is a specific form of cell death that is important for normal development and tissue homeostasis. Caspases are critical executioners of apoptosis, and living cells prevent their inappropriate activation through inhibitor of apoptosis proteins (IAPs). In Drosophila, caspase activation depends on the IAP antagonists, Reaper (Rpr), Head involution defective (Hid), and Grim. These proteins share a common motif to bind Drosophila IAP1 (DIAP1) and have partially redundant functions. We now show that IAP antagonists physically interact with each other. Rpr is able to self-associate and also binds to Hid and Grim. We have defined the domain involved in self-association and demonstrate that it is critical for cell-killing activity in vivo. In addition, we show that Rpr requires Hid for recruitment to the mitochondrial membrane and for efficient induction of cell death in vivo. Both targeting of Rpr to mitochondria and forced dimerization strongly promotes apoptosis. Our results reveal the functional importance of a previously unrecognized multimeric IAP antagonist complex for the induction of apoptosis.
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spelling pubmed-31015952011-06-06 Drosophila IAP antagonists form multimeric complexes to promote cell death Sandu, Cristinel Ryoo, Hyung Don Steller, Hermann J Cell Biol Research Articles Apoptosis is a specific form of cell death that is important for normal development and tissue homeostasis. Caspases are critical executioners of apoptosis, and living cells prevent their inappropriate activation through inhibitor of apoptosis proteins (IAPs). In Drosophila, caspase activation depends on the IAP antagonists, Reaper (Rpr), Head involution defective (Hid), and Grim. These proteins share a common motif to bind Drosophila IAP1 (DIAP1) and have partially redundant functions. We now show that IAP antagonists physically interact with each other. Rpr is able to self-associate and also binds to Hid and Grim. We have defined the domain involved in self-association and demonstrate that it is critical for cell-killing activity in vivo. In addition, we show that Rpr requires Hid for recruitment to the mitochondrial membrane and for efficient induction of cell death in vivo. Both targeting of Rpr to mitochondria and forced dimerization strongly promotes apoptosis. Our results reveal the functional importance of a previously unrecognized multimeric IAP antagonist complex for the induction of apoptosis. The Rockefeller University Press 2010-09-20 /pmc/articles/PMC3101595/ /pubmed/20837774 http://dx.doi.org/10.1083/jcb.201004086 Text en © 2010 Sandu et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Sandu, Cristinel
Ryoo, Hyung Don
Steller, Hermann
Drosophila IAP antagonists form multimeric complexes to promote cell death
title Drosophila IAP antagonists form multimeric complexes to promote cell death
title_full Drosophila IAP antagonists form multimeric complexes to promote cell death
title_fullStr Drosophila IAP antagonists form multimeric complexes to promote cell death
title_full_unstemmed Drosophila IAP antagonists form multimeric complexes to promote cell death
title_short Drosophila IAP antagonists form multimeric complexes to promote cell death
title_sort drosophila iap antagonists form multimeric complexes to promote cell death
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101595/
https://www.ncbi.nlm.nih.gov/pubmed/20837774
http://dx.doi.org/10.1083/jcb.201004086
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