title: SIPAR negatively regulates STAT3 signaling and inhibits progression of melanoma.
abstract: Persistently activated STAT3 is important for tumorigenesis in a variety of cancers, including melanoma. Although many co-factors in the regulation of STAT3 activity have been identified, it remains unclear how STAT3 phosphorylation is negatively regulated. Here, we report that SIPAR (STAT3-Interacting Protein As a Repressor) inhibits STAT3 activity by accelerating its dephosphorylation. We observed that SIPAR directly interacted with STAT3 upon IL-6 stimulation. Moreover, over-expression of SIPAR reduced, whereas depletion enhanced, the level of phosphorylated STAT3. We further demonstrated that SIPAR inhibited the growth of melanoma cells by decreasing the level of phosphorylated STAT3 and the expression of its target genes. These results suggest that SIPAR, functioning as a new negative regulator, inhibits STAT3 activity by enhancing its dephosphorylation and represses melanoma progression.
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.forename: Fuqin
authors.initials: F
authors.lastname: Su
authors.forename: Hongxiu
authors.initials: H
authors.lastname: Ning
authors.forename: Yangmeng
authors.initials: Y
authors.lastname: Wang
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Geng
authors.forename: Yarui
authors.initials: Y
authors.lastname: Feng
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Wang
authors.forename: Yanquan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhe
authors.initials: Z
authors.lastname: Jin
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Baoqing
authors.initials: B
authors.lastname: Jia
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Chang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D008546:Melanoma, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D047368:Tumor Burden
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C545285:Fam220a protein, mouse; D015850:Interleukin-6; D009687:Nuclear Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D008156:Luciferases
keywords: Dephosphorylation; Melanoma; SIPAR; STAT3