RSRC1 SUMOylation enhances SUMOylation and inhibits transcriptional activity of estrogen receptor ß.

The transcription factor estrogen receptor ß (ERß) plays roles in the central nervous, endocrine, cardiovascular, and immune systems. ERß can be SUMOylated. However, the underlying mechanism remains unclear. Here, we show that RSRC1/SRrp53 interacts with ERß and SUMOylation of RSRC1 is required for regulation of PIAS1-mediated ERß SUMOylation. RSRC1 promotes ERß SUMOylation through enhanced interaction between ERß and PIAS1. RSRC1 represses ERß transcriptional activity through regulation of ERß SUMOylation. By establishing RSRC1 as a novel cofactor for SUMOylation, our data provide insight into regulation of ERß SUMOylation and indicate that SUMOylation of one protein can regulate another protein SUMOylation.