Ligand-dependent transcription of estrogen receptor α is mediated by the ubiquitin ligase EFP

Estrogen-mediated ubiquitylation and subsequent degradation of the estrogen receptor α (ERα) appears to be involved in the transcriptional activity of ERα. We show that the estrogen-responsive finger protein (EFP) interacts with and ubiquitylates ERα. EFP promoted the ubiquitylation of ERαin vitro and in vivo and consequently promoted the degradation of ERα. The interaction between EFP and ERα was greatly enhanced in the presence of estrogen. The action of EFP on ERα in the presence of estrogen resulted in a robust interaction between ERα and Tip60, one of the transcriptional coactivators, leading to activation of ERα transcriptional activity. However, a dominant negative mutant of EFP lacking the RING domain prolonged the half-life of ERα and inhibited the transcription by ERα. Our results indicate that EFP functions as a cofactor for ERα-mediated transcription, thus suggesting that ERα-mediated transcription is closely linked to the ubiquitylation of ERα.