Repression of transcriptional activity of estrogen receptor alpha by a Cullin3/SPOP ubiquitin E3 ligase complex.

The role of SPOP in the ubiquitination of ER alpha by the Cullin3-based E3 ubiquitin ligase complex was investigated. We showed that the N-terminal region of SPOP containing the MATH domain interacts with the AF-2 domain of ER alpha in cultured human embryonic 293 cells. SPOP was required for coimmunoprecipitation of ER alpha; with Cullin3. This is the first report of the essential role of SPOP in ERalpha ubiquitination by the Cullin3-based E3 ubiquitin ligase complex. We also demonstrated repression of the transactivation capability of ER alpha; in cultured mammalian cells.