Estrogen receptors alpha and beta form heterodimers on DNA
Estrogen receptors alpha and beta form heterodimers on DNA
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DOI：
10.1074/jbc.272.32.19858
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发表时间：
1997-08-08
影响因子：
4.8
通讯作者：
Parker, MG
中科院分区：
文献类型：
--
作者：
Cowley, SM;Hoare, S;Parker, MG
雌激素受体(ER)以两种形式表达，ERα和ERβ。在这里，我们证明了在体外和体内表达的ERα和ERβ形成了与DNA结合的异二聚体，其亲和力(K-d约为2 nM)与ERα相似，但大于ERβ同源二聚体。对ERα激素结合域的突变分析表明，与ERβ形成同源二聚体所需的二聚化界面非常相似，但不完全相同，异源二聚体和同源二聚体一样，在与DNA结合时能够与类固醇受体辅活化子1结合，并刺激报告基因在转基因细胞中的转录，考虑到ERα和ERβ在组织中的相对表达以及ERα/ERβ和ERβ之间DNA结合活性的差异，似乎异二聚体在一组靶细胞中具有功能活性。
The estrogen receptor (ER) is expressed in two forms, ER alpha and ER beta. Here we show that ER alpha and ER beta, expressed both in vitro and in vivo, form heterodimers which bind to DNA with an affinity (K-d of approximately 2 nM) similar to that of ER alpha and greater than that of ER beta homodimers. Mutation analysis of the hormone binding domain of ER alpha suggests that the dimerization interface required to form heterodimers with ER beta is very similar but not identical to that required for homodimer formation, The heterodimer, like the homodimers, are capable of binding the steroid receptor coactivator-1 when bound to DNA and stimulating transcription of a reporter gene in transfected cells, Given the relative expression of ER alpha and ER beta in tissues and the difference in DNA binding activity between ER alpha/ER beta heterodimers and ER beta it seems Likely that the heterodimer is functionally active in a subset of target cells.