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Updated: Jul 5, 2026

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Inducible and Reversible Dominant-negative (DN) Protein Inhibition
Published on: January 7, 2019
通过类固醇受体介导的老鼠益生菌基因表达的抑制不需要受体的DNA结合域
1Center for Molecular Genetics, University of California, San Diego, La Jolla 92093-0613.
Cell
|March 11, 1988
概括
葡萄糖皮质类药物和雌激素通过涉及雌激素受体的独特机制来抑制益乳基因表达. 这些类固醇激素与Pit-1等转录因子相互作用,调节基因活性.
科学领域:
- 分子内分泌学分子内分泌学
- 基因规则 基因规则
- 类固醇激素的作用 类固醇激素的作用
背景情况:
- 益生素基因表达是一种复杂的过程,受各种因素的调节,包括类固醇激素.
- 葡萄糖皮质类药物是已知的前乳素基因表达的负调节剂.
- 雌激素的调节作用取决于环境,受特定的DNA元素的影响.
研究的目的:
- 阐明葡萄糖皮质醇和雌激素调节前素基因表达的分子机制.
- 为了确定负责转录抑制的雌激素受体内的特定域.
- 研究转录因子 (如Pit-1) 在调解类固醇激素效应中的作用.
主要方法:
- 对雌激素受体的突变分析以界定功能域.
- 混合受体的构建,以评估特定受体区域的抑制能力.
- 分析大鼠前素5'-边缘基因组区域,以确定cis-活性元素.
- 电泳运动转移试验用于研究转录因子结合.
主要成果:
- 以雌激素受体为媒介抑制前素基因表达,需要一个独特的63氨基酸区域 (251-314),与DNA结合和类固醇结合域分开.
- 葡萄糖皮质体受体中的类似区域对混合受体具有抑制活性.
- 益生素基因的5'-侧翼区域含有多个元素,它们结合转录因子Pit-1,通过雌激素和葡萄皮质激素对抑制进行介导.
- 雌激素受体的积极和消极的转录效应是由单独的功能域介导的.
结论:
- 雌激素受体具有不同的结构域用于转录激活和抑制.
- 类固醇激素受体和其他转录因子 (如Pit-1) 之间的蛋白质与蛋白质相互作用对于调解对前素基因表达的抑制作用至关重要.
- 类固醇激素对前素的调节涉及受体领域, cis 调节元素和转录因子之间的复杂相互作用.
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