Ligand-dependent transcription of estrogen receptor α is mediated by the ubiquitin ligase EFP
Ligand-dependent transcription of estrogen receptor α is mediated by the ubiquitin ligase EFP
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DOI：
10.1016/j.bbrc.2007.03.134
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发表时间：
2007-05-25
影响因子：
3.1
通讯作者：
Hatakeyama, Shigetsugu
中科院分区：
文献类型：
--
作者：
Nakajima, Ayako;Maruyama, Satoru;Hatakeyama, Shigetsugu
雌激素介导的泛素化和随后的雌激素受体α（ER α）的降解似乎参与了ER α的转录活性。我们发现雌激素反应指蛋白（EFP）与ER α相互作用并使其泛素化。EFP在体内外均能促进ER α的泛素化，从而促进ER α的降解。EFP和ER α之间的相互作用在雌激素的存在下大大增强。在雌激素存在下EFP对ER α的作用导致ER α和Tip60（转录共激活因子之一）之间的强烈相互作用，导致ER α转录活性的激活。然而，缺失RING结构域的EFP显性负突变体延长了ER α的半衰期并抑制了ER α的转录。我们的研究结果表明，EFP作为ER α介导的转录的辅因子，从而表明ER α介导的转录与ER α的泛素化密切相关。(c)2007年爱思唯尔公司All rights reserved.
Estrogen-mediated ubiquitylation and subsequent degradation of the estrogen receptor alpha (ER alpha) appears to be involved in the transcriptional activity of ER alpha. We show that the estrogen-responsive finger protein (EFP) interacts with and ubiquitylates ER alpha. EFP promoted the ubiquitylation of ER alpha in vitro and in vivo and consequently promoted the degradation of ER alpha. The interaction between EFP and ER alpha was greatly enhanced in the presence of estrogen. The action of EFP on ER alpha in the presence of estrogen resulted in a robust interaction between ER alpha and Tip60, one of the transcriptional coactivators, leading to activation of ER alpha transcriptional activity. However, a dominant negative mutant of EFP lacking the RING domain prolonged the half-life of ER alpha and inhibited the transcription by ER alpha. Our results indicate that EFP functions as a cofactor for ER alpha-mediated transcription, thus suggesting that ER alpha-mediated transcription is closely linked to he ubiquitylation of ER alpha. (c) 2007 Elsevier Inc. All rights reserved.