Dimerization modulates the activity of the orphan nuclear receptor ERRγ
Dimerization modulates the activity of the orphan nuclear receptor ERRγ
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DOI：
10.1016/j.bbrc.2003.12.194
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发表时间：
2004-02-20
影响因子：
3.1
通讯作者：
Aarnisalo, P
中科院分区：
文献类型：
--
作者：
Huppunen, J;Aarnisalo, P
雌激素相关受体γ（ERRgamma）是一种缺乏已鉴定的天然配体的孤儿核受体。然而，最近显示4-羟基他莫昔芬和己烯雌酚结合并抑制ERR γ活性。ERR作为单体组成性地激活转录。我们在这里表明，ERRgamma形式也通过其配体结合域的二聚体。同源二聚化增强转录活性。相反，与相关受体ERRa的异源二聚化抑制ERRa和ERRa的活性。反向ERR γ激动剂4 OHT进一步抑制ERR γ-ERR α异二聚体的活性，表明4 OHT可能通过ERR γ调节ERR α信号传导。因此，受体二聚化调节ERR的转录活性。(C)2004年爱思唯尔公司All rights reserved.
Estrogen-related receptor gamma (ERRgamma) is an orphan nuclear receptor lacking identified natural ligands. However, 4-hydroxytamoxifen and diethylstilbestrol were recently shown to bind to and inhibit ERRgamma activity. ERR activates transcription constitutively as a monomer. We show here that ERRgamma forms also dimers via its ligand-binding domain. Homodimerization enhances the transcriptional activity. In contrast, heterodimerization with the related receptor ERRalpha inhibits the activities of both ERRgamma and ERRa. The inverse ERRgamma agonist 4OHT further inhibits the activity of the ERRgamma-ERRalpha heterodimer, indicating that 4OHT may modulate ERRalpha signaling via ERRgamma. Receptor dimerization thus modulates the transcriptional activities of ERRs. (C) 2004 Elsevier Inc. All rights reserved.