一个新型的cis元素通过c-ErbA调解连接体独立激活:对荷尔蒙调节的影响
F Saatcioglu1, T Deng, M Karin
1Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla 92093-0636.
Cell
|December 17, 1993
概括
一种新的激素反应元件 (HRE) 在没有甲状腺激素 (T3) 的情况下强烈激活,而T3则逆转了效果. 这种独特的元素证明了c-ErbAα受体对选择性激活域的使用.
科学领域:
- 分子生物学分子生物学
- 内分泌学 在内分泌学.
- 病毒学 病毒学
背景情况:
- 经典的激素反应元件 (HREs) 通常需要连接物结合来激活受体.
- 甲状腺激素 (T3) 受体,如c-ErbAα,是参与基因调节的核受体.
研究的目的:
- 描述一种新的HRE,RSV-T3RE及其与甲状腺激素受体的相互作用.
- 为了研究c-ErbA alpha的依赖联体和独立激活机制.
主要方法:
- 记者基因测定用于测量转录激活.
- 对受体-DNA相互作用和形状变化的分析.
- 对c-ErbAα激活域的突变分析.
主要成果:
- RSV-T3RE通过c-ErbAalpha调解强的连接体独立激活,由T3.3逆转.
- c-ErbAα同位体和c-ErbAα/视网膜X受体 (RXR) 异位体激活RSV-T3RE.
- 连接体独立激活涉及N端域,而连接体依赖激活需要C端域.
结论:
- RSV-T3RE代表了一种具有独特监管特性的新型HRE类.
- c-ErbAα表现出基于HRE和配体状态的选择性激活域部署.
- 这一发现为甲状腺激素受体功能和基因调节提供了新的见解.
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