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.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [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]
第一作者机构：[1]Tongji Univ, Shanghai Peoples Hosp 10, Dept Clin Lab Med, Shanghai 200072, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Tongji Univ, Shanghai Peoples Hosp 10, Dept Clin Lab Med, Shanghai 200072, Peoples R China[*1]3rd FL,Bldg 1,301,Middle Yanchang Rd, Shanghai 200072, Peoples R China
推荐引用方式(GB/T 7714)：
Xu Shanshan,Tong Minghong,Huang Jingqin,et al.TRIB2 inhibits Wnt/beta-Catenin/TCF4 signaling through its associated ubiquitin E3 ligases, beta-TrCP, COP1 and Smurf1, in liver cancer cells[J].FEBS LETTERS.2014,588(23):4334-4341.doi:10.1016/j.febslet.2014.09.042.
APA：
Xu, Shanshan,Tong, Minghong,Huang, Jingqin,Zhang, Yue,Qiao, Yongxia...&Sun, Fenyong.(2014).TRIB2 inhibits Wnt/beta-Catenin/TCF4 signaling through its associated ubiquitin E3 ligases, beta-TrCP, COP1 and Smurf1, in liver cancer cells.FEBS LETTERS,588,(23)
MLA：
Xu, Shanshan,et al."TRIB2 inhibits Wnt/beta-Catenin/TCF4 signaling through its associated ubiquitin E3 ligases, beta-TrCP, COP1 and Smurf1, in liver cancer cells".FEBS LETTERS 588..23(2014):4334-4341
