title: USP5 Is Dispensable for Monoubiquitin Maintenance in Drosophila.
abstract: Ubiquitination is a post-translational modification that regulates most cellular pathways and processes, including degradation of proteins by the proteasome. Substrate ubiquitination is controlled at various stages, including through its reversal by deubiquitinases (DUBs). A critical outcome of this process is the recycling of monoubiquitin. One DUB whose function has been proposed to include monoubiquitin recycling is USP5. Here, we investigated whether Drosophila USP5 is important for maintaining monoubiquitin in vivo We found that the fruit fly orthologue of USP5 has catalytic preferences similar to its human counterpart and that this DUB is necessary during fly development. Our biochemical and genetic experiments indicate that reduction of USP5 does not lead to monoubiquitin depletion in developing flies. Also, introduction of exogenous ubiquitin does not suppress developmental lethality caused by loss of endogenous USP5. Our work indicates that a primary physiological role of USP5 is not to recycle monoubiquitin for reutilization, but that it may involve disassembly of conjugated ubiquitin to maintain proteasome function.
authors.affiliation: From the Departments of Pharmacology and.
authors.forename: Gorica
authors.initials: G
authors.lastname: Ristic
authors.affiliation: From the Departments of Pharmacology and.
authors.forename: Wei-Ling
authors.initials: WL
authors.lastname: Tsou
authors.affiliation: From the Departments of Pharmacology and.
authors.forename: Ermal
authors.initials: E
authors.lastname: Guzi
authors.affiliation: the Department of Biochemistry and the Neuroscience Research Center, Medical College of Wisconsin, Milwaukee Wisconsin 53226.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Kanack
authors.affiliation: the Department of Biochemistry and the Neuroscience Research Center, Medical College of Wisconsin, Milwaukee Wisconsin 53226.
authors.forename: Kenneth Matthew
authors.initials: KM
authors.lastname: Scaglione
authors.affiliation: From the Departments of Pharmacology and Neurology, Wayne State University School of Medicine, Detroit, Michigan 48201 and stodi@med.wayne.edu.
authors.forename: Sokol V
authors.initials: SV
authors.lastname: Todi
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*; D064570:Ubiquitin-Specific Proteases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D025801:Ubiquitin; C000593006:USP5 protein, Drosophila; D064570:Ubiquitin-Specific Proteases; D046988:Proteasome Endopeptidase Complex
keywords: 70 kilodalton heat shock protein (Hsp70); CHIP; Drosophila; deubiquitylation (deubiquitination); post-translational modification (PTM); protease; proteasome; ubiquitin