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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Bibliographic Details
Published in:PloS one 2012-08, Vol.7 (8), p.e43112-e43112
Main Authors: Tsou, Wei-Ling, Sheedlo, Michael J, Morrow, Marie E, Blount, Jessica R, McGregor, Kelly M, Das, Chittaranjan, Todi, Sokol V
Format: Article
Language:English
Subjects:
Adults
Amino acids
Analysis
Animals
Apoptosis
Ataxia
Biology
Cell division
Cellular structure
Developmental stages
Drosophila
Drosophila melanogaster - enzymology
Drosophila Proteins - metabolism
Endopeptidases - metabolism
Enzymes
Genetic aspects
Genomes
Glial cells
Health aspects
Homeostasis
Humans
Insects
Medicine
Mutation
Neurology
Neuronal-glial interactions
Pharmacology
Physiological aspects
Physiology
Post-translation
Proteases
Proteins
Redundancy
Ubiquitin
Ubiquitin - metabolism
Ubiquitination
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0043112