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>