GdX/UBL4A Specifically Stabilizes the TC45/STAT3 Association and Promotes Dephosphorylation of STAT3 to Repress Tumorigenesis

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• 作者：Yangmeng Wang¹ ; ¹¹ ; Hongxiu Ning¹ ; ² ; ¹¹ ; Fangli Ren¹ ; ¹¹ ; Yuanjiang Zhang¹ ; ¹¹ ; Yu Rong¹ ; Yinyin Wang¹ ; Fuqin Su¹ ; Chenguang Cai¹ ; Zhe Jin¹ ; Zhiyong Li¹ ; Xinqi Gong¹ ; Yonggong Zhai³ ; Dianjun Wang⁴ ; Baoqing Jia⁴ ; Ying Qiu¹ ; Yasuhiko Tomita⁵ ; Joseph J.Y. Sung⁶ ; Jun Yu⁶ ; David M. Irwin⁷ ; Xiao Yang⁸ ; Xinyuan Fu⁹ ; Y. Eugene Chin¹⁰ ; ^{yechin@sibs.ac.cn" class="auth_mail} ; Zhijie Chang¹ ; ^{zhijiec@tsinghua.edu.cn" class="auth_mail}
• 刊名：Molecular Cell
• 出版年：6 March, 2014
• 年：2014
• 卷：53
• 期：5
• 页码：752-765
• 全文大小：5636 K

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Summary

Impaired phosphatase activity contributes to the persistent activation of STAT3 in tumors. Given that STAT family members with various or even opposite functions are often phosphorylated or dephosphorylated by the same enzymes, the mechanism for STAT3-specific dephosphorylation in cells remains largely unknown. Here, we report that GdX (UBL4A) promotes STAT3 dephosphorylation via mediating the interaction between TC45 (the nuclear isoform of TC-PTP) and STAT3 specifically. GdX stabilizes the TC45-STAT3 complex to bestow upon STAT3 an efficient dephosphorylation by TC45. Inasmuch, GdX suppresses tumorigenesis and tumor development by reducing the level of phospho-STAT3 (p-STAT3), whereas deletion of GdX results in a high level of p-STAT3 and accelerated colorectal tumorigenesis induced by AOM/DSS. Thus, GdX converts TC45, a nonspecific phosphatase, into a STAT3-specific phosphatase by bridging an association between TC45 and STAT3.