由雌激素受体激活卵白蛋白基因涉及到-俊复合体
M P Gaub1, M Bellard, I Scheuer
1Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Faculté de Médecine, Strasbourg, France.
Cell
|December 21, 1990
概括
卵蛋白促进剂的促进者
科学领域:
- 分子生物学分子生物学
- 基因规则 基因规则
- 内分泌学 在内分泌学.
背景情况:
- 卵泡蛋白基因促进体有一个对雌激素反应的元素 (ERE),对雌激素受体 (ER) 进行细胞特异激活至关重要.
- 了解荷尔蒙信号和其他途径如何汇聚到基因促进器是解读复杂生物调节的关键.
研究的目的:
- 研究由雌激素和其他信号通路调节卵蛋白基因的分子机制.
- 识别与卵蛋白 (ERE) 结合的蛋白质及其在转录激活中的作用.
主要方法:
- 卵蛋白促进剂ERE的局部定向突变发生.
- 电泳运动转移试验 (EMSAs) 检测蛋白质-DNA相互作用.
- 记者基因测试 (转染) 用于测量促进体活性.
- 使用截断的ER结构分析蛋白质-蛋白质和蛋白质-DNA相互作用.
主要成果:
- 卵蛋白ERE与核蛋白复合体结合,包括蛋白c-Fos和c-Jun,独立于ER和雌激素.
- 消除雌激素诱导性的ERE中的突变也可以防止复杂的形成.
- ERE序列 (5'-TGGGTCA-3') 对于醇诱导至关重要,并且是c-Fos和c-Jun的目标.
- c-Fos,c-Jun和ER共同激活卵白蛋白促进体,而ER的DNA结合域对于这种共同激活是不可用的.
结论:
- 激素诱导和信号传导途径在转录水平上汇聚在卵蛋白促进体上.
- 该ER与转录因子c-Fos和c-Jun合作调节卵蛋白基因表达,突出显示信号通路的复杂相互作用.
- 在同激活中ER的作用表明了独立于直接DNA结合的机制,可能涉及与c-Fos/c-Jun复合体的蛋白质-蛋白质相互作用.
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