title: Nuclear termination of STAT3 signaling through SIPAR (STAT3-Interacting Protein As a Repressor)-dependent recruitment of T cell tyrosine phosphatase TC-PTP.
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.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Fangli
authors.initials: F
authors.lastname: Ren
authors.affiliation: Structure Biology, Memorial Sloan Kettering Cancer Centre, New York 10065, USA.
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Geng
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Minami
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yarui
authors.initials: Y
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Xuanzi
authors.initials: X
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yangmeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Mengdi
authors.initials: M
authors.lastname: Li
authors.affiliation: Institute of Immunology, The Third Military Medical University, Chongqing 400038, China. Electronic address: jun-li04@mails.tsinghua.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Chang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C545285:Fam220a protein, mouse; D009687:Nuclear Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; C516649:PTPN2 protein, human; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2; C516653:Ptpn2 protein, mouse
keywords: Dephosphorylation; Protein tyrosine phosphatase; STAT3; STAT3-Interacting Protein As a Repressor; T cell protein tyrosine phosphatase TC45