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

Abstract

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 ER alpha ubiquitination by the Cullin3-based E3 ubiquitin ligase complex. We also demonstrated repression of the transactivation capability of ER alpha in cultured mammalian cells.