Activation of estrogen receptor α by raloxifene through an activating protein-1-dependent tethering mechanism in human cervical epithelial cancer cells: a role for c-Jun N-terminal kinase.
Activation of estrogen receptor α by raloxifene through an activating protein-1-dependent tethering mechanism in human cervical epithelial cancer cells: a role for c-Jun N-terminal kinase.
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DOI：
10.1016/j.mce.2011.09.032
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发表时间：
2012-01-02
影响因子：
4.1
通讯作者：
Kraus, W. Lee
中科院分区：
文献类型：
--
作者：
Fogarty, Elizabeth A.;Matulis, Christina K.;Kraus, W. Lee
关键词：
核雌激素受体α（ERα）通过两种不同的机制调节靶基因对配体的反应表达：直接结合DNA和通过其他DNA结合转录因子（例如AP-1）间接束缚。在本文所述的研究中，我们检查了选择性雌激素受体调节剂（SERM）雷洛昔芬（Ral）激活AP-1拴系通路中ERα的分子机制。我们的研究结果与MMP 1和PRUNE基因表明，c-Fos组件的AP-1拴系因子和c-Jun N-末端激酶1（JNK 1）组成性结合在启动子区域之前，Ral曝光。然后Ral以c-Fos依赖性方式促进ERα在启动子处的结合。有趣的是，我们发现JNK 1酶活性是通过ERα激活Ral依赖性基因所必需的。我们的研究结果表明，RAR依赖性ERα募集到AP-1结合位点的一个作用是刺激JNK 1酶活性。另外，Ral占据的ERα可能募集蛋白质底物与启动子结合的JNK 1结合，而JNK 1活性无任何变化。总的来说，我们的研究揭示了JNK 1在ERα决定基因调控结果中的新作用。
Nuclear estrogen receptor α (ERα) regulates target gene expression in response to ligands through two distinct mechanisms: direct binding to DNA and indirect tethering through other DNA-bound transcription factors, such as AP-1. In the studies described herein, we examined the molecular mechanisms underlying the activation of ERα in the AP-1 tethering pathway by the selective estrogen receptor modulator (SERM) raloxifene (Ral). Our results with the MMP1 and PRUNE genes indicate that the c-Fos component of the AP-1 tethering factor and the c-Jun N-terminal kinase 1 (JNK1) are constitutively bound at the promoter regions prior to Ral exposure. Ral then promotes the binding of ERα at the promoter in a c-Fos-dependent manner. Interestingly, we found that JNK1 enzymatic activity is required for Ral-dependent gene activation through ERα. Our results suggest that one role for Ral-dependent recruitment of ERα to the AP-1 binding site is to stimulate JNK1 enzymatic activity. Alternatively, Ral-occupied ERα might recruit protein substrates to promoter-bound JNK1 without any change in JNK1 activity. Collectively, our studies have revealed a new role for JNK1 in determining gene regulatory outcomes by ERα.
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影响因子：
4
作者：
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通讯作者：
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DOI：
10.1073/pnas.251194298
发表时间：
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影响因子：
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DOI：
10.1073/pnas.0407113102
发表时间：
2005-01-18
影响因子：
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作者：
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通讯作者：
Kraus, WL
影响因子：
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作者：
Heldring, Nina;Isaacs, Gary D.;Kraus, W. Lee
通讯作者：
Kraus, W. Lee