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J Biol Chem. 2016 Apr 22;291(17):9161-72. doi: 10.1074/jbc.M115.703504. Epub 2016 Feb 25.

USP5 Is Dispensable for Monoubiquitin Maintenance in Drosophila.

Author information

1
From the Departments of Pharmacology and.
2
the Department of Biochemistry and the Neuroscience Research Center, Medical College of Wisconsin, Milwaukee Wisconsin 53226.
3
From the Departments of Pharmacology and Neurology, Wayne State University School of Medicine, Detroit, Michigan 48201 and stodi@med.wayne.edu.

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.

KEYWORDS:

70 kilodalton heat shock protein (Hsp70); CHIP; Drosophila; deubiquitylation (deubiquitination); post-translational modification (PTM); protease; proteasome; ubiquitin

PMID:
26917723
PMCID:
PMC4861482
DOI:
10.1074/jbc.M115.703504
[Indexed for MEDLINE]
Free PMC Article

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