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Deubiquitinase USP47/UBP64E Regulates ?-Catenin Ubiquitination and Degradation
and Plays a Positive Role in Wnt Signaling
#MMPMID26169834
Shi J
; Liu Y
; Xu X
; Zhang W
; Yu T
; Jia J
; Liu C
Mol Cell Biol
2015[Oct]; 35
(19
): 3301-11
PMID26169834
show ga
Wnt signaling plays important roles in development and tumorigenesis. A central
question about the Wnt pathway is the regulation of ?-catenin. Phosphorylation of
?-catenin by CK1? and GSK3 promotes ?-catenin binding to ?-TrCP, leading to
?-catenin degradation through the proteasome. The phosphorylation and
ubiquitination of ?-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 ?-catenin ubiquitination. Inactivation of USP47 by RNAi increased
?-catenin ubiquitination, attenuated Wnt signaling, and repressed cancer cell
growth. Furthermore, USP47 deubiquitinates itself, whereas ?-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.
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