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SCFβ-TRCP E3 ubiquitin ligase targets the tumor suppressor ZNRF3 for ubiquitination and degradation.

Authors :
Ci, Yanpeng
Li, Xiaoning
Chen, Maorong
Zhong, Jiateng
North, Brian J.
Inuzuka, Hiroyuki
He, Xi
Li, Yu
Guo, Jianping
Dai, Xiangpeng
Source :
Protein & Cell; Oct2018, Vol. 9 Issue 10, p879-889, 11p
Publication Year :
2018

Abstract

Wnt signaling has emerged as a major regulator of tissue development by governing the self-renewal and maintenance of stem cells in most tissue types. As a key upstream regulator of the Wnt pathway, the transmembrane E3 ligase ZNRF3 has recently been established to play a role in negative regulation of Wnt signaling by targeting Frizzled (FZD) receptor for ubiquitination and degradation. However, the upstream regulation of ZNRF3, in particular the turnover of ZNRF3, is still unclear. Here we report that ZNRF3 is accumulated in the presence of proteasome inhibitor treatment independent of its E3-ubiquitin ligase activity. Furthermore, the Cullin 1-specific SCF complex containing β-TRCP has been identified to directly interact with and ubiquitinate ZNRF3 thereby regulating its protein stability. Similar with the degradation of β-catenin by β-TRCP, ZNRF3 is ubiquitinated by β-TRCP in both CKI-phosphorylation- and degron-dependent manners. Thus, our findings not only identify a novel substrate for β-TRCP oncogenic regulation, but also highlight the dual regulation of Wnt signaling by β-TRCP in a context-dependent manner where β-TRCP negatively regulates Wnt signaling by targeting β-catenin, and positively regulates Wnt signaling by targeting ZNRF3. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
1674800X
Volume :
9
Issue :
10
Database :
Complementary Index
Journal :
Protein & Cell
Publication Type :
Academic Journal
Accession number :
132021566
Full Text :
https://doi.org/10.1007/s13238-018-0510-2