GdX/UBL4A specifically stabilizes the TC45/STAT3 association and promotes dephosphorylation of STAT3 to repress tumorigenesis

Yangmeng Wang, Hongxiu Ning, Fangli Ren, Yuanjiang Zhang, Yu Rong, Yinyin Wang, Fuqin Su, Chenguang Cai, Zhe Jin, Zhiyong Li, Xinqi Gong, Yonggong Zhai, Dianjun Wang, Baoqing Jia, Ying Qiu, Yasuhiko Tomita, Joseph J.Y. Sung, Jun Yu, David M. Irwin, Xiao YangXinyuan Fu, Y. Eugene Chin, Zhijie Chang

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)752-765
Number of pages14
JournalMolecular Cell
Volume53
Issue number5
DOIs
StatePublished - Mar 6 2014
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Wang, Y., Ning, H., Ren, F., Zhang, Y., Rong, Y., Wang, Y., Su, F., Cai, C., Jin, Z., Li, Z., Gong, X., Zhai, Y., Wang, D., Jia, B., Qiu, Y., Tomita, Y., Sung, J. J. Y., Yu, J., Irwin, D. M., ... Chang, Z. (2014). GdX/UBL4A specifically stabilizes the TC45/STAT3 association and promotes dephosphorylation of STAT3 to repress tumorigenesis. Molecular Cell, 53(5), 752-765. https://doi.org/10.1016/j.molcel.2014.01.020