Journal article
WDR20 Regulates Activity of the USP12 center dot UAF1 Deubiquitinating Enzyme Complex
The Journal of biological chemistry, Vol.285(15), pp.11252-11257
04/09/2010
DOI: 10.1074/jbc.M109.095141
PMCID: PMC2857003
PMID: 20147737
Abstract
The UAF1 (Usp1-associated factor 1) protein binds and stimulates three deubiquitinating enzymes: USP1, USP12, and USP46. Although the USP1 center dot UAF1 complex is required for regulation of the Fanconi anemia (FA) DNA repair pathway, less is known about the USP12 center dot UAF1 and the USP46 center dot UAF1 complexes. To understand further the nature of the USP12 and USP46 complexes, we attempted to identify proteins that interact with the USP12 and USP46 deubiquitinating enzyme complexes. We identified WDR20, a WD40-repeat containing protein, as a common binding partner of UAF1, USP12, and USP46. Further analysis showed that WDR20 associates exclusively with USP12 and USP46, not with USP1. Furthermore, we demonstrate the purification of a ternary USP12 center dot UAF1 center dot WDR20 complex. Interestingly, and consistent with the binding assays, WDR20 stimulated the enzymatic activity of USP12 center dot UAF1, but not of USP1 center dot UAF1. Consistent with our previous report that USP12 and USP46 do not regulate the FA pathway, small interference RNA-mediated depletion of WDR20 protein did not affect the FA pathway or DNA damage responses. We provide a model in which WDR20 serves as a stimulatory subunit for preserving and regulating the activity of the subset of the UAF1 center dot USP complexes.
Details
- Title: Subtitle
- WDR20 Regulates Activity of the USP12 center dot UAF1 Deubiquitinating Enzyme Complex
- Creators
- Younghoon Kee - Harvard UniversityKailin Yang - Dana-Farber Cancer InstituteMartin A. Cohn - Dana-Farber Cancer InstituteWilhelm Haas - Harvard UniversitySteven P. Gygi - Harvard UniversityAlan D. D'Andrea - Harvard University
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.285(15), pp.11252-11257
- Publisher
- Amer Soc Biochemistry Molecular Biology Inc
- DOI
- 10.1074/jbc.M109.095141
- PMID
- 20147737
- PMCID
- PMC2857003
- eISSN
- 1083-351X
- Number of pages
- 6
- Grant note
- R01HL052725 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R01DK043889 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) R01DK43889; R01HL52725; P01CA092584; U19A1067751 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P01CA092584 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 04/09/2010
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984696570702771
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