葡萄糖皮质体受体的DNA结合对于生存并不是必不可少的
H M Reichardt1, K H Kaestner, J Tuckermann
1Division of Molecular Biology of the Cell I, German Cancer Research Center, Heidelberg.
Cell
|May 30, 1998
概括
葡萄糖皮质体受体 (GR) 使用DNA结合和非DNA结合机制来调节基因. 在GR中发生的一种特定突变 (A458T) 揭示了其DNA结合独立功能的生存在体内至关重要的重要性.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 内分泌学 在内分泌学.
背景情况:
- 葡萄糖皮质体受体 (GR) 在细胞功能和生存中起着至关重要的作用.
- 通过DNA结合依赖和独立的途径,GR调节基因转录.
研究的目的:
- 区分和评估GR的DNA结合依赖与独立的转录活动的体内意义.
- 研究受损GR二分化对转录调节的功能后果.
主要方法:
- 在小鼠中使用Cre/loxP系统生成GR基因中的特定点突变 (A458T).
- 由此产生的GRdim突变小鼠的特征分析,以分析GR功能 in vivo.
- 在GRdim突变体中评估GRE依赖的交换活化和AP-1驱动的基因转抑制.
主要成果:
- A458T突变破坏了GR的二分化,损害了GRE依赖的交换活化.
- 独立于DNA结合的功能,如AP-1基因的转抑制,在GRdim突变中仍然具有功能.
- 与GR-/-小鼠不同,GRdim小鼠是可行的,这突显了DNA结合独立的GR活动的重要作用.
结论:
- 独立于DNA结合的机制对于体内功能和通过葡萄糖皮质体受体介导的生存至关重要.
- 该研究成功地分离并证明了活体中不同GR调节通路的相关性.
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