Conjugation of Complex Polyubiquitin Chains to WRNIP1

Bish, R. A., Fregoso, O. I., Piccini, A., Myers, M. P. (August 2008) Conjugation of Complex Polyubiquitin Chains to WRNIP1. J Proteome Res, 7 (8). 3481-3489 .

URL: http://www.ncbi.nlm.nih.gov/pubmed/18613717
DOI: 10.1021/pr800217q

Abstract

Werner helicase interacting protein 1 (WRNIP1) is a ubiquitin-binding protein that undergoes extensive post-translational modification including ubiquitination, sumoylation, and phosphorylation. These post-translational modifications are expected to regulate the function of WRNIP1 in the DNA damage response. In this study, we use a denaturing tandem affinity purification technique along with mass spectrometry to show that, unlike most ubiquitin-binding proteins, WRNIP1 is polyubiquitinated. WRNIP1 polyubiquitination is reminiscent of the well-characterized phenomenon of the coupled monoubiquitination of ubiquitin-binding proteins in that this polyubiquitination is dependent on the presence of an intact ubiquitin-binding domain. The polyubiquitin chains conjugated to WRNIP1 are linked through lysines 11, 48, and 63. This study presents the first evidence for the conjugation of K11-K48-K63 polyubiquitin chains to a specific substrate in vivo. Polyubiquitination is likely to regulate WRNIP1's function in the DNA damage response, as UV radiation induces the hyperubiquitination of WRNIP1. Polyubiquitination with noncanonical intraubiquitin linkages may represent a unique mode of regulation of UBZ domain-containing proteins.

Item Type: Paper
Uncontrolled Keywords: WRNIP1 UBZ ubiquitin mass spectrometry proteomics degradation proteasome post-translational modification monoubiquitination polyubiquitination
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > ubiquitin ligase
CSHL Authors:
Communities: CSHL labs > Myers lab
Watson School > Publications
Depositing User: Matt Covey
Date: August 2008
Date Deposited: 28 Feb 2013 15:21
Last Modified: 22 Sep 2014 15:47
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27506

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