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SIPAR negatively regulates STAT3 signaling and inhibits progression of melanoma

Authors :
Yanquan Zhang
Zhijie Chang
Zhe Jin
Fuqin Su
Fangli Ren
Hongxiu Ning
Yarui Feng
Yi Li
Baoqing Jia
Yinyin Wang
Yongtao Geng
Yangmeng Wang
Source :
Cellular signalling. 25(11)
Publication Year :
2013

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.

Details

ISSN :
18733913
Volume :
25
Issue :
11
Database :
OpenAIRE
Journal :
Cellular signalling
Accession number :
edsair.doi.dedup.....ff06b72c54d8d2a9d50df51b77bac439