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Systematic Analysis of the Physiological Importance of Deubiquitinating Enzymes

Deubiquitinating enzymes (DUBs) are proteases that control the post-translational modification of proteins by ubiquitin and in turn regulate diverse cellular pathways. Despite a growing understanding of DUB biology at the structural and molecular level, little is known about the physiological import...

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Autores principales: Tsou, Wei-Ling, Sheedlo, Michael J., Morrow, Marie E., Blount, Jessica R., McGregor, Kelly M., Das, Chittaranjan, Todi, Sokol V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427330/
https://www.ncbi.nlm.nih.gov/pubmed/22937016
http://dx.doi.org/10.1371/journal.pone.0043112
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author Tsou, Wei-Ling
Sheedlo, Michael J.
Morrow, Marie E.
Blount, Jessica R.
McGregor, Kelly M.
Das, Chittaranjan
Todi, Sokol V.
author_facet Tsou, Wei-Ling
Sheedlo, Michael J.
Morrow, Marie E.
Blount, Jessica R.
McGregor, Kelly M.
Das, Chittaranjan
Todi, Sokol V.
author_sort Tsou, Wei-Ling
collection PubMed
description Deubiquitinating enzymes (DUBs) are proteases that control the post-translational modification of proteins by ubiquitin and in turn regulate diverse cellular pathways. Despite a growing understanding of DUB biology at the structural and molecular level, little is known about the physiological importance of most DUBs. Here, we systematically identify DUBs encoded by the genome of Drosophila melanogaster and examine their physiological importance in vivo. Through domain analyses we uncovered 41 Drosophila DUBs, most of which have human orthologues. Systematic knockdown of the vast majority of DUBs throughout the fly or in specific cell types had dramatic consequences for Drosophila development, adult motility or longevity. Specific DUB subclasses proved to be particularly necessary during development, while others were important in adults. Several DUBs were indispensable in neurons or glial cells during developmental stages; knockdown of others perturbed the homeostasis of ubiquitinated proteins in adult flies, or had adverse effects on wing positioning as a result of neuronal requirements. We demonstrate the physiological significance of the DUB family of enzymes in intact animals, find that there is little functional redundancy among members of this family of proteases, and provide insight for future investigations to understand DUB biology at the molecular, cellular and organismal levels.
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spelling pubmed-34273302012-08-30 Systematic Analysis of the Physiological Importance of Deubiquitinating Enzymes Tsou, Wei-Ling Sheedlo, Michael J. Morrow, Marie E. Blount, Jessica R. McGregor, Kelly M. Das, Chittaranjan Todi, Sokol V. PLoS One Research Article Deubiquitinating enzymes (DUBs) are proteases that control the post-translational modification of proteins by ubiquitin and in turn regulate diverse cellular pathways. Despite a growing understanding of DUB biology at the structural and molecular level, little is known about the physiological importance of most DUBs. Here, we systematically identify DUBs encoded by the genome of Drosophila melanogaster and examine their physiological importance in vivo. Through domain analyses we uncovered 41 Drosophila DUBs, most of which have human orthologues. Systematic knockdown of the vast majority of DUBs throughout the fly or in specific cell types had dramatic consequences for Drosophila development, adult motility or longevity. Specific DUB subclasses proved to be particularly necessary during development, while others were important in adults. Several DUBs were indispensable in neurons or glial cells during developmental stages; knockdown of others perturbed the homeostasis of ubiquitinated proteins in adult flies, or had adverse effects on wing positioning as a result of neuronal requirements. We demonstrate the physiological significance of the DUB family of enzymes in intact animals, find that there is little functional redundancy among members of this family of proteases, and provide insight for future investigations to understand DUB biology at the molecular, cellular and organismal levels. Public Library of Science 2012-08-24 /pmc/articles/PMC3427330/ /pubmed/22937016 http://dx.doi.org/10.1371/journal.pone.0043112 Text en © 2012 Tsou et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Tsou, Wei-Ling
Sheedlo, Michael J.
Morrow, Marie E.
Blount, Jessica R.
McGregor, Kelly M.
Das, Chittaranjan
Todi, Sokol V.
Systematic Analysis of the Physiological Importance of Deubiquitinating Enzymes
title Systematic Analysis of the Physiological Importance of Deubiquitinating Enzymes
title_full Systematic Analysis of the Physiological Importance of Deubiquitinating Enzymes
title_fullStr Systematic Analysis of the Physiological Importance of Deubiquitinating Enzymes
title_full_unstemmed Systematic Analysis of the Physiological Importance of Deubiquitinating Enzymes
title_short Systematic Analysis of the Physiological Importance of Deubiquitinating Enzymes
title_sort systematic analysis of the physiological importance of deubiquitinating enzymes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427330/
https://www.ncbi.nlm.nih.gov/pubmed/22937016
http://dx.doi.org/10.1371/journal.pone.0043112
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