SCFβ-TRCP E3 ubiquitin ligase targets the tumor suppressor ZNRF3 for ubiquitination and degradation
| العنوان: | SCFβ-TRCP E3 ubiquitin ligase targets the tumor suppressor ZNRF3 for ubiquitination and degradation |
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| المؤلفون: | Hiroyuki Inuzuka, Yanpeng Ci, Xiaoning Li, Jianping Guo, Brian J. North, Jiateng Zhong, Xiangpeng Dai, Maorong Chen, Yu Li, Xi He |
| المصدر: | Protein & Cell Protein & Cell, Vol 9, Iss 10, Pp 879-889 (2018) |
| بيانات النشر: | Higher Education Press, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Frizzled, Ubiquitin-Protein Ligases, Regulator, lcsh:Animal biochemistry, Biochemistry, 03 medical and health sciences, Wnt, SCF complex, Ubiquitin, Drug Discovery, Humans, Ligase activity, lcsh:QH573-671, CKI, lcsh:QP501-801, Cells, Cultured, biology, Chemistry, lcsh:Cytology, ZNRF3, Wnt signaling pathway, Ubiquitination, Cell Biology, beta-Transducin Repeat-Containing Proteins, β-TRCP, Ubiquitin ligase, Cell biology, 030104 developmental biology, Proteolysis, biology.protein, Cullin, Biotechnology, Research Article |
| الوصف: | 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. Electronic supplementary material The online version of this article (10.1007/s13238-018-0510-2) contains supplementary material, which is available to authorized users. |
| اللغة: | English |
| تدمد: | 1674-8018 1674-800X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ee2a1cf113ae84c6e73b2a6e78f5f6f1 http://europepmc.org/articles/PMC6160385 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....ee2a1cf113ae84c6e73b2a6e78f5f6f1 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 16748018 1674800X |
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