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.
Document Type
Article
Publication Date
10-2015
Digital Object Identifier (DOI)
http://dx.doi.org/10.1128/MCB.00373-15
Funding Information
J.J. was supported by R01GM079684 and C.L. was supported by R01CA172379 from the National Institutes of Health.
Repository Citation
Shi, Jiandang; Liu, Yajuan; Xu, Xuehe; Zhang, Wen; Yu, Tianxin; Jia, Jianhang; and Liu, Chunming, "Deubiquitinase USP47/UBP64E Regulates β-Catenin Ubiquitination and Degradation and Plays a Positive Role in Wnt Signaling" (2015). Markey Cancer Center Faculty Publications. 60.
https://uknowledge.uky.edu/markey_facpub/60
Notes/Citation Information
Published in Molecular and Cellular Biology, v. 35, no. 19, p. 3301-3311.
Copyright © 2015, American Society for Microbiology. All Rights Reserved.
The copyright holders have granted the permission for posting the article here.