Suppressive effect of aryl hydrocarbon receptor repressor on transcriptional activity of estrogen receptor alpha by protein-protein interaction in stably and transiently expressing cell lines
Suppressive effect of aryl hydrocarbon receptor repressor on transcriptional activity of estrogen receptor alpha by protein-protein interaction in stably and transiently expressing cell lines
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DOI：
10.1016/j.mce.2008.05.004
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发表时间：
2008-09-10
影响因子：
4.1
通讯作者：
Inouye, Yoshio
中科院分区：
文献类型：
--
作者：
Kanno, Yuichiro;Takane, Yusuke;Inouye, Yoshio
芳烃受体阻遏物（AhRR）以配体非依赖性方式抑制雌激素受体α（ER α）在瞬时转染试验中增强异源雌激素应答报告质粒转录的能力，以及人乳腺癌MCF-7细胞中内源性雌激素应答基因的转录。AhRR通过变构干扰AF-1的配体非依赖性功能来抑制ER α介导的反式激活。AhRR和ER α之间的直接相互作用在ER α的多组分结合位点，其范围从DNA结合域到配体结合域，但不包括AF-1部分，通过免疫共沉淀试验证实。AhRR/ER α复合物形成于细胞核隔室中，并通过染色质免疫沉淀试验确定，被E2-应答基因的启动子中的顺式元件捕获。AhRR可能对ER α同源二聚体的转录活性起辅助抑制作用。(c)2008爱思唯尔爱尔兰有限公司保留所有权利。
Aryl hydrocarbon receptor repressor (AhRR) suppressed, in a ligand independent manner, the ability of estrogen receptor alpha (ER alpha) to enhance the transcription of heterologous estrogen-responsive reporter plasmids in transient transfection assays, as well as of endogenous estrogen-responsive genes in human breast cancer MCF-7 cells. AhRR repressed ER alpha-mediated trans-activation by interfering allosterically with the ligand-independent function of AF-1. The direct interaction between AhRR and ER alpha at the multipartite binding site of ER alpha, which ranges from a DNA binding domain to a ligand binding domain, but did not include the AF-1 moiety was confirmed by a coimmunoprecipitation assay. The AhRR/ER alpha complex was formed in the nuclear compartment and was entrapped by a cis-element in the promote:c of E2-responsive genes, as determined in a chromatin immunoprecipitation assay. AhRR might play a role of co-repressor on the transcriptional activity of the ER alpha homodimer. (c) 2008 Elsevier Ireland Ltd. All rights reserved.