Journal
FEBS LETTERS
Volume 588, Issue 23, Pages 4334-4341Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2014.09.042
Keywords
Protein stability; Wnt/beta-Catenin signaling; Ubiquitination; Liver cancer
Funding
- National Natural Science Foundation of China [81301689, 81201884]
- Shanghai Committee of Science and Technology (Yangfan project) [14YF1412300]
- Young College Teachers' Training Scheme of Shanghai [ZZjdyx13007]
- Tongji University (Outstanding youth training program) [1501219080]
- Shanghai Tenth People's Hospital (Climbing training program) [04.01.13024, 04.01.13049]
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Tribbles homolog 2 (TRIB2) is specifically regulated by Wnt signaling in liver cancer cells but not in colon cancer cells. However, whether and how TRIB2 regulates Wnt signaling in liver cancer cells remains unclear. Here, we report that TRIB2 negatively regulates Wnt activity through a reduction in protein stability of TCF4 and beta-Catenin. Mechanistically, TRIB2 associated-ubiquitin E3 ligases beta-transducin repeat-containing E3 ubiquitin protein ligase (beta-TrCP), COP1 and Smad ubiquitination regulatory factor 1 (Smurf1) reduced TCF4/beta-Catenin expression, and these effects could be enhanced by TRIB2. Moreover, deletion of the binding regions of these E3-ligases within the TRIB2 protein decreased ubiquitination of TCF4/beta-Catenin and reduced nuclear accumulation of beta-TrCP, COP1 and Smurf1, which suggested that TRIB2 regulated-Wnt activity is closely correlated with its associated E3 ligases. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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