Drosophila IAP1-mediated ubiquitylation controls activation of the initiator caspase DRONC independent of protein degradation.

Ubiquitylation targets proteins for proteasome-mediated degradation and plays important roles in many biological processes including apoptosis. However, non-proteolytic functions of ubiquitylation are also known. In Drosophila, the inhibitor of apoptosis protein 1 (DIAP1) is known to ubiquitylate th...

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Autores principales:	Tom V Lee, Yun Fan, Shiuan Wang, Mayank Srivastava, Meike Broemer, Pascal Meier, Andreas Bergmann
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/bc434fd8b28545628097a25934903ea0
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spelling	oai:doaj.org-article:bc434fd8b28545628097a25934903ea02021-11-18T06:17:04ZDrosophila IAP1-mediated ubiquitylation controls activation of the initiator caspase DRONC independent of protein degradation.1553-73901553-740410.1371/journal.pgen.1002261https://doaj.org/article/bc434fd8b28545628097a25934903ea02011-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21909282/pdf/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Ubiquitylation targets proteins for proteasome-mediated degradation and plays important roles in many biological processes including apoptosis. However, non-proteolytic functions of ubiquitylation are also known. In Drosophila, the inhibitor of apoptosis protein 1 (DIAP1) is known to ubiquitylate the initiator caspase DRONC in vitro. Because DRONC protein accumulates in diap1 mutant cells that are kept alive by caspase inhibition ("undead" cells), it is thought that DIAP1-mediated ubiquitylation causes proteasomal degradation of DRONC, protecting cells from apoptosis. However, contrary to this model, we show here that DIAP1-mediated ubiquitylation does not trigger proteasomal degradation of full-length DRONC, but serves a non-proteolytic function. Our data suggest that DIAP1-mediated ubiquitylation blocks processing and activation of DRONC. Interestingly, while full-length DRONC is not subject to DIAP1-induced degradation, once it is processed and activated it has reduced protein stability. Finally, we show that DRONC protein accumulates in "undead" cells due to increased transcription of dronc in these cells. These data refine current models of caspase regulation by IAPs.Tom V LeeYun FanShiuan WangMayank SrivastavaMeike BroemerPascal MeierAndreas BergmannPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 7, Iss 9, p e1002261 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Tom V Lee Yun Fan Shiuan Wang Mayank Srivastava Meike Broemer Pascal Meier Andreas Bergmann Drosophila IAP1-mediated ubiquitylation controls activation of the initiator caspase DRONC independent of protein degradation.
description	Ubiquitylation targets proteins for proteasome-mediated degradation and plays important roles in many biological processes including apoptosis. However, non-proteolytic functions of ubiquitylation are also known. In Drosophila, the inhibitor of apoptosis protein 1 (DIAP1) is known to ubiquitylate the initiator caspase DRONC in vitro. Because DRONC protein accumulates in diap1 mutant cells that are kept alive by caspase inhibition ("undead" cells), it is thought that DIAP1-mediated ubiquitylation causes proteasomal degradation of DRONC, protecting cells from apoptosis. However, contrary to this model, we show here that DIAP1-mediated ubiquitylation does not trigger proteasomal degradation of full-length DRONC, but serves a non-proteolytic function. Our data suggest that DIAP1-mediated ubiquitylation blocks processing and activation of DRONC. Interestingly, while full-length DRONC is not subject to DIAP1-induced degradation, once it is processed and activated it has reduced protein stability. Finally, we show that DRONC protein accumulates in "undead" cells due to increased transcription of dronc in these cells. These data refine current models of caspase regulation by IAPs.
format	article
author	Tom V Lee Yun Fan Shiuan Wang Mayank Srivastava Meike Broemer Pascal Meier Andreas Bergmann
author_facet	Tom V Lee Yun Fan Shiuan Wang Mayank Srivastava Meike Broemer Pascal Meier Andreas Bergmann
author_sort	Tom V Lee
title	Drosophila IAP1-mediated ubiquitylation controls activation of the initiator caspase DRONC independent of protein degradation.
title_short	Drosophila IAP1-mediated ubiquitylation controls activation of the initiator caspase DRONC independent of protein degradation.
title_full	Drosophila IAP1-mediated ubiquitylation controls activation of the initiator caspase DRONC independent of protein degradation.
title_fullStr	Drosophila IAP1-mediated ubiquitylation controls activation of the initiator caspase DRONC independent of protein degradation.
title_full_unstemmed	Drosophila IAP1-mediated ubiquitylation controls activation of the initiator caspase DRONC independent of protein degradation.
title_sort	drosophila iap1-mediated ubiquitylation controls activation of the initiator caspase dronc independent of protein degradation.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/bc434fd8b28545628097a25934903ea0
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Drosophila IAP1-mediated ubiquitylation controls activation of the initiator caspase DRONC independent of protein degradation.

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