Multiple Sequence- Specific DNA-Binding Proteins Mediate Estrogen Receptor Signaling through a Tethering Pathway
Multiple Sequence- Specific DNA-Binding Proteins Mediate Estrogen Receptor Signaling through a Tethering Pathway
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DOI：
10.1210/me.2010-0425
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发表时间：
2011-04-01
影响因子：
--
通讯作者：
Kraus, W. Lee
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文献类型：
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作者：
Heldring, Nina;Isaacs, Gary D.;Kraus, W. Lee
雌激素受体（er）通过其他DNA结合的转录因子（如激活蛋白1）间接募集（tethering）到DNA上是雌激素信号通路的重要组成部分，但我们对这一途径中配体依赖性激活的机制了解有限。通过蛋白质组学、基因组学和基因特异性分析，我们证明了大量dna结合转录因子通过栓系途径参与雌激素信号传导。此外，我们还定义了一组内源性基因，通过激活蛋白1（如c-Fos）和cAMP反应元件结合蛋白家族成员介导ER α栓系介导雌激素反应。最后，我们发现c-Fos和cAMP反应元件结合蛋白1之间的功能相互作用有助于通过栓系途径进行雌激素依赖性调节。基于我们的研究结果，我们得出结论，拴链途径中的ER α募集依赖于配体诱导的转录因子复合物的形成，该复合物涉及来自不同蛋白质家族的转录因子之间的相互作用。（Molecular Endocrinology 25:564-574, 2011）
The indirect recruitment (tethering) of estrogen receptors (ERs) to DNA through other DNA-bound transcription factors (e.g. activator protein 1) is an important component of estrogen-signaling pathways, but our understanding of the mechanisms of ligand-dependent activation in this pathway is limited. Using proteomic, genomic, and gene-specific analyses, we demonstrate that a large repertoire of DNA-binding transcription factors contribute to estrogen signaling through the tethering pathway. In addition, we define a set of endogenous genes for which ER alpha tethering through activator protein 1 (e.g. c-Fos) and cAMP response element-binding protein family members mediates estrogen responsiveness. Finally, we show that functional interplay between c-Fos and cAMP response element-binding protein 1 contributes to estrogen-dependent regulation through the tethering pathway. Based on our results, we conclude that ER alpha recruitment in the tethering pathway is dependent on the ligand-induced formation of transcription factor complexes that involves interplay between the transcription factors from different protein families. (Molecular Endocrinology 25:564-574, 2011)