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Nuclear termination of STAT3 signaling through SIPAR (STAT3‐Interacting Protein As a Repressor)‐dependent recruitment of T cell tyrosine phosphatase TC‐PTP
Author(s) -
Ren Fangli,
Geng Yongtao,
Minami Takayuki,
Qiu Ying,
Feng Yarui,
Liu Chunxiao,
Zhao Juan,
Wang Yinyin,
Fan Xuanzi,
Wang Yangmeng,
Li Mengdi,
Li Jun,
Chang Zhijie
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.05.031
Subject(s) - dephosphorylation , protein tyrosine phosphatase , stat3 , phosphorylation , microbiology and biotechnology , phosphatase , tyrosine phosphorylation , repressor , biology , cell growth , chemistry , biochemistry , transcription factor , gene
STAT3 is associated with embryo development and survival as well as proliferation and metastasis of tumor cells. In a previous study, we demonstrated that STAT3‐Interacting Protein As a Repressor (SIPAR) enhances the dephosphorylation of STAT3 and negatively regulates its activity. However, it remains unclear how SIPAR inhibits phosphorylation of STAT3. Here we demonstrate that SIPAR directly interacts with T cell protein tyrosine phosphatase TC45 and enhances its association with STAT3. This interaction triggers an accelerated dephosphorylation process for STAT3. Furthermore, SIPAR inhibits the transcriptional activity of STAT3 in wild‐type MEF cells but not in TC45 null MEF cells. These results suggest that SIPAR terminates the activation of STAT3 through a dephosphorylation process that is dependent upon interaction with TC45 in the nucleus.