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Publication : SIPAR negatively regulates STAT3 signaling and inhibits progression of melanoma.

First Author  Ren F Year  2013
Journal  Cell Signal Volume  25
Issue  11 Pages  2272-80
PubMed ID  23917203 Mgi Jnum  J:354403
Mgi Id  MGI:7734797 Doi  10.1016/j.cellsig.2013.07.023
Citation  Ren F, et al. (2013) SIPAR negatively regulates STAT3 signaling and inhibits progression of melanoma. Cell Signal 25(11):2272-80
abstractText  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.
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