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The deubiquitinating enzyme USP36 controls selective autophagy activation by ubiquitinated proteins
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Taillebourg, Emmanuel, Gregoire, Isabel, Viargues, Perrine, Jacomin, Anne-Claire, Thevenon, Dominique, Faure, Mathias and Fauvarque, Marie-Odile (2012) The deubiquitinating enzyme USP36 controls selective autophagy activation by ubiquitinated proteins. Autophagy, 8 (5). pp. 767-779. doi:10.4161/auto.19381 ISSN 1554-8627.
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Official URL: http://dx.doi.org/10.4161/auto.19381
Abstract
Initially described as a nonspecific degradation process induced upon starvation, autophagy is now known also to be involved in the degradation of specific ubiquitinated substrates such as mitochondria, bacteria and aggregated proteins, ensuring crucial functions in cell physiology and immunity. We report here that the deubiquitinating enzyme USP36 controls selective autophagy activation in Drosophila and in human cells. We show that dUsp36 loss of function autonomously inhibits cell growth while activating autophagy. Despite the phenotypic similarity, dUSP36 is not part of the TOR signaling pathway. Autophagy induced by dUsp36 loss of function depends on p62/SQSTM1, an adaptor for delivering cargo marked by polyubiquitin to autophagosomes. Consistent with p62 requirement, dUsp36 mutant cells display nuclear aggregates of ubiquitinated proteins, including Histone H2B, and cytoplasmic ubiquitinated proteins; the latter are eliminated by autophagy. Importantly, USP36 function in p62-dependent selective autophagy is conserved in human cells. Our work identifies a novel, crucial role for a deubiquitinating enzyme in selective autophagy.
Item Type: | Journal Article | ||||
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Subjects: | Q Science > QH Natural history Q Science > QP Physiology |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||
Library of Congress Subject Headings (LCSH): | Cell death, Ubiquitin | ||||
Journal or Publication Title: | Autophagy | ||||
Publisher: | Landes Bioscience | ||||
ISSN: | 1554-8627 | ||||
Official Date: | 1 May 2012 | ||||
Dates: |
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Volume: | 8 | ||||
Number: | 5 | ||||
Page Range: | pp. 767-779 | ||||
DOI: | 10.4161/auto.19381 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access | ||||
Funder: | Institut national de la santé et de la recherche médicale (France) (INSERM), Cluster de recherche en infectiologie de la région Centre (France) [Cluster 10 Infectiologie], Rhône-Alpes (France : Region) | ||||
Grant number: | ANR-O8-JCJC-0064-01 (INSERM) |
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