title: Ligand-dependent transcription of estrogen receptor alpha is mediated by the ubiquitin ligase EFP.
abstract: Estrogen-mediated ubiquitylation and subsequent degradation of the estrogen receptor alpha (ERalpha) appears to be involved in the transcriptional activity of ERalpha. We show that the estrogen-responsive finger protein (EFP) interacts with and ubiquitylates ERalpha. EFP promoted the ubiquitylation of ERalphain vitro and in vivo and consequently promoted the degradation of ERalpha. The interaction between EFP and ERalpha was greatly enhanced in the presence of estrogen. The action of EFP on ERalpha in the presence of estrogen resulted in a robust interaction between ERalpha and Tip60, one of the transcriptional coactivators, leading to activation of ERalpha transcriptional activity. However, a dominant negative mutant of EFP lacking the RING domain prolonged the half-life of ERalpha and inhibited the transcription by ERalpha. Our results indicate that EFP functions as a cofactor for ERalpha-mediated transcription, thus suggesting that ERalpha-mediated transcription is closely linked to the ubiquitylation of ERalpha.
authors.affiliation: Department of Molecular Biochemistry, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido 060-8638, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Nakajima
authors.forename: Satoru
authors.initials: S
authors.lastname: Maruyama
authors.forename: Miyuki
authors.initials: M
authors.lastname: Bohgaki
authors.forename: Naoto
authors.initials: N
authors.lastname: Miyajima
authors.forename: Tadasuke
authors.initials: T
authors.lastname: Tsukiyama
authors.forename: Noriaki
authors.initials: N
authors.lastname: Sakuragi
authors.forename: Shigetsugu
authors.initials: S
authors.lastname: Hatakeyama
mesh_terms: D002460:Cell Line; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008024:Ligands; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D047628:Estrogen Receptor alpha; D008024:Ligands; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin; C084523:TRIM25 protein, human; D044767:Ubiquitin-Protein Ligases