Nakajima Ayako, Maruyama Satoru, Bohgaki Miyuki, Miyajima Naoto, Tsukiyama Tadasuke, Sakuragi Noriaki, Hatakeyama Shigetsugu
Department of Molecular Biochemistry, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido 060-8638, Japan.
Biochem Biophys Res Commun. 2007 May 25;357(1):245-51. doi: 10.1016/j.bbrc.2007.03.134. Epub 2007 Mar 30.
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.
雌激素介导的雌激素受体α（ERα）泛素化及随后的降解似乎与ERα的转录活性有关。我们发现雌激素反应性指蛋白（EFP）与ERα相互作用并使其泛素化。EFP在体外和体内均促进ERα的泛素化，进而促进ERα的降解。在雌激素存在的情况下，EFP与ERα之间的相互作用显著增强。雌激素存在时EFP对ERα的作用导致ERα与转录共激活因子之一Tip60之间产生强烈相互作用，从而激活ERα的转录活性。然而，缺乏RING结构域的EFP显性负突变体延长了ERα的半衰期并抑制了ERα的转录。我们的结果表明EFP作为ERα介导转录的辅因子发挥作用，因此提示ERα介导的转录与ERα的泛素化密切相关。
