10.1371/journal.pone.0043112 Wei-Ling Tsou Wei-Ling Tsou Michael J. Sheedlo Michael J. Sheedlo Marie E. Morrow Marie E. Morrow Jessica R. Blount Jessica R. Blount Kelly M. McGregor Kelly M. McGregor Chittaranjan Das Chittaranjan Das Sokol V. Todi Sokol V. Todi Systematic Analysis of the Physiological Importance of Deubiquitinating Enzymes Public Library of Science 2012 systematic physiological deubiquitinating enzymes 2012-08-24 00:17:37 Dataset https://plos.figshare.com/articles/dataset/Systematic_Analysis_of_the_Physiological_Importance_of_Deubiquitinating_Enzymes/121057 <div><p>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 <em>Drosophila melanogaster</em> and examine their physiological importance <em>in vivo</em>. Through domain analyses we uncovered 41 <em>Drosophila</em> 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 <em>Drosophila</em> 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.</p> </div>