PMID:26026268

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
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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

References

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