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FEBS Lett. 2015 Jul 8;589(15):1890-6. doi: 10.1016/j.febslet.2015.05.031. Epub 2015 May 27.

Nuclear termination of STAT3 signaling through SIPAR (STAT3-Interacting Protein As a Repressor)-dependent recruitment of T cell tyrosine phosphatase TC-PTP.

Author information

1
State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences, Tsinghua University, Beijing 100084, China.
2
Structure Biology, Memorial Sloan Kettering Cancer Centre, New York 10065, USA.
3
Institute of Immunology, The Third Military Medical University, Chongqing 400038, China. Electronic address: jun-li04@mails.tsinghua.edu.cn.
4
State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: zhijiec@tsinghua.edu.cn.

Abstract

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.

KEYWORDS:

Dephosphorylation; Protein tyrosine phosphatase; STAT3; STAT3-Interacting Protein As a Repressor; T cell protein tyrosine phosphatase TC45

PMID:
26026268
DOI:
10.1016/j.febslet.2015.05.031
[Indexed for MEDLINE]
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