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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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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. |
format | Online Article Text |
id | pubmed-3427330 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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