Ubiquitination directly enhances activity of the deubiquitinating enzyme ataxin-3. EMBO J 2009 Feb 18;28(4):372-82
Date
01/21/2009Pubmed ID
19153604Pubmed Central ID
PMC2646149DOI
10.1038/emboj.2008.289Scopus ID
2-s2.0-60549100850 (requires institutional sign-in at Scopus site) 149 CitationsAbstract
Deubiquitinating enzymes (DUBs) control the ubiquitination status of proteins in various cellular pathways. Regulation of the activity of DUBs, which is critically important to cellular homoeostasis, can be achieved at the level of gene expression, protein complex formation, or degradation. Here, we report that ubiquitination also directly regulates the activity of a DUB, ataxin-3, a polyglutamine disease protein implicated in protein quality control pathways. Ubiquitination enhances ubiquitin (Ub) chain cleavage by ataxin-3, but does not alter its preference for K63-linked Ub chains. In cells, ubiquitination of endogenous ataxin-3 increases when the proteasome is inhibited, when excess Ub is present, or when the unfolded protein response is induced, suggesting that the cellular functions of ataxin-3 in protein quality control are modulated through ubiquitination. Ataxin-3 is the first reported DUB in which ubiquitination directly regulates catalytic activity. We propose a new function for protein ubiquitination in regulating the activity of certain DUBs and perhaps other enzymes.
Author List
Todi SV, Winborn BJ, Scaglione KM, Blount JR, Travis SM, Paulson HLMESH terms used to index this publication - Major topics in bold
AnimalsAtaxin-3
Brain
COS Cells
Catalysis
Gene Expression Regulation
Homeostasis
Humans
Machado-Joseph Disease
Models, Biological
Nerve Tissue Proteins
Nuclear Proteins
Protein Denaturation
Protein Folding
Protein Processing, Post-Translational
Repressor Proteins
Ubiquitin
