Affiliation:
1. Markey Cancer Center, University of Kentucky, Lexington, Kentucky, USA
2. Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky, USA
Abstract
ABSTRACT
Wnt signaling plays important roles in development and tumorigenesis. A central question about the Wnt pathway is the regulation of β-catenin. Phosphorylation of β-catenin by CK1α and GSK3 promotes β-catenin binding to β-TrCP, leading to β-catenin degradation through the proteasome. The phosphorylation and ubiquitination of β-catenin have been well characterized; however, it is unknown whether and how a deubiquitinase is involved. In this study, by screening RNA interference (RNAi) libraries, we identified USP47 as a deubiquitinase that prevents β-catenin ubiquitination. Inactivation of USP47 by RNAi increased β-catenin ubiquitination, attenuated Wnt signaling, and repressed cancer cell growth. Furthermore, USP47 deubiquitinates itself, whereas β-TrCP promotes USP47 ubiquitination through interaction with an atypical motif in USP47. Finally,
in vivo
studies in the
Drosophila
wing suggest that UBP64E, the USP47 counterpart in
Drosophila
, is required for Armadillo stabilization and plays a positive role in regulating Wnt target gene expression.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Cited by
65 articles.
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