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.
|Number of pages||9|
|State||Published - Nov 2013|
Bibliographical noteFunding Information:
This work was supported by grants from the 973 Project ( 2011CB910502 ), NSFC ( 30871286 , 31071225 , 31030040 ), Tsinghua Science Foundation ( 20121080018 ), and the 863 Project ( 2012AA021703 ) in China. We thank Dr. David M Irwin from the University of Toronto for his editing of the manuscript.
ASJC Scopus subject areas
- Cell Biology