在蛋白c-Jun和葡萄糖皮质类受体之间的功能对抗
R Schüle1, P Rangarajan, S Kliewer
1Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, California 92037.
Cell
|September 21, 1990
概括
葡萄糖皮质体受体 (GR) 和Jun/AP-1转录因子相互抑制对方的基因激活. 这种新的抑制机制涉及蛋白质相互作用,而不是DNA结合,影响基因调节.
科学领域:
- 分子生物学分子生物学
- 基因规则 基因规则
- 转录因子 转录因子
背景情况:
- 葡萄糖皮质体受体 (GR) 和Jun/AP-1是参与细胞过程的关键转录因子.
- 了解它们的相互作用对于破译复杂的基因调节网络至关重要.
研究的目的:
- 调查GR和Jun/AP-1之间的监管关系.
- 阐明这些因素相互影响转录活动的机制.
主要方法:
- 对c-Jun和GR的过度表达研究.
- 基因激活的分析使用记者测定与葡萄糖皮质体反应元素 (GREs).
- 对GR和c-Jun域的突变分析.
- 凝延迟测试用于评估DNA-蛋白质复合体的形成.
主要成果:
- 过度表达c-Jun阻断了GR中介基因激活在GREs.
- GR抑制了AP-1驱动的转录激活.
- GR的带结合和DNA结合域以及c-Jun的氨酸拉链区域对于抑制至关重要.
- 细菌表达的c-Jun干扰了GR与GREs的结合.
结论:
- GR和Jun/AP-1表现出转录激活的相互抑制.
- 这种相互作用是由一个独立于直接DNA结合的新型机制介导的,可能涉及蛋白质-蛋白质相互作用.
- 这些发现揭示了通过不同的转录因子类调节基因表达的新层复杂性.
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