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PMID:26026268

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Citation

Ren, F, Geng, Y, Minami, T, Qiu, Y, Feng, Y, Liu, C, Zhao, J, Wang, Y, Fan, X, Wang, Y, Li, M, Li, J and Chang, Z (2015) Nuclear termination of STAT3 signaling through SIPAR (STAT3-Interacting Protein As a Repressor)-dependent recruitment of T cell tyrosine phosphatase TC-PTP. FEBS Lett. 589:1890-6

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.

Links

PubMed Online version:10.1016/j.febslet.2015.05.031

Keywords

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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:STAT3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q3ZN08

F

Seeded From UniProt

complete

MOUSE:STAT3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q06180

F

Seeded From UniProt

complete

MOUSE:PTN2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q3ZN08

F

Seeded From UniProt

complete

MOUSE:PTN2

acts_upstream_of_or_within

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q3ZN08

P

  • has_regulation_target:(MGI:MGI:103038)

Seeded From UniProt

complete

MOUSE:PTN2

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:PTN2

acts_upstream_of_or_within

GO:0006470: protein dephosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PTN2

acts_upstream_of_or_within

GO:0006470: protein dephosphorylation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1914488

P

Seeded From UniProt

complete

MOUSE:PTN2

enables

GO:0097677: STAT family protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P42227

F

Seeded From UniProt

complete

MOUSE:F220A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q06180

F

Seeded From UniProt

complete

MOUSE:F220A

acts_upstream_of_or_within

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q06180

P

  • has_regulation_target:(MGI:MGI:103038)

Seeded From UniProt

complete

MOUSE:F220A

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:F220A

acts_upstream_of_or_within

GO:0032092: positive regulation of protein binding

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • regulates_o_has_input:(MGI:MGI:103038)
  • regulates_o_has_input:(MGI:MGI:97806)

Seeded From UniProt

complete

MOUSE:F220A

acts_upstream_of_or_within

GO:0006470: protein dephosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(MGI:MGI:103038)

Seeded From UniProt

complete

MOUSE:F220A

acts_upstream_of_or_within

GO:0006470: protein dephosphorylation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:97806

P

  • has_input:(MGI:MGI:103038)

Seeded From UniProt

complete

MOUSE:F220A

enables

GO:0097677: STAT family protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P42227

F

Seeded From UniProt

complete

MOUSE:STAT3

enables

GO:0000981: DNA-binding transcription factor activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:STAT3

acts_upstream_of_or_within

GO:0042789: mRNA transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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