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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Nucleus / metabolism*
  • Cells, Cultured
  • HEK293 Cells
  • Humans
  • Mice
  • Nuclear Proteins / metabolism*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2 / metabolism*
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction*


  • Adaptor Proteins, Signal Transducing
  • Fam220a protein, mouse
  • Nuclear Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Stat3 protein, mouse
  • PTPN2 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2
  • Ptpn2 protein, mouse