通过与一般转录因子TFIIH结合和通过CDK7酸化刺激RARα激活功能AF-1
C Rochette-Egly1, S Adam, M Rossignol
1Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université Louis Pasteur, Collège de France, Illkirch, Strasbourg.
Cell
|July 11, 1997
概括
网酸受体α (RARα) 的活性取决于Ser-77的酸化. 循环素依赖性激酶7 (CDK7) 和转录因子TFIIH结合并酸化RARαα,增强其交换活化功能.
科学领域:
- 分子生物学分子生物学
- 基因规则 基因规则
- 蛋白质酸化是指蛋白质的酸化.
背景情况:
- 视网膜酸受体α (RARα) 的N端激活功能AF-1对其活性至关重要.
- 化特定残留物,如Ser-77,可以调节RARα的功能.
研究的目的:
- 为了研究Ser-77酸化在RARα转激活中的作用.
- 在体内和体外确定负责Ser-77酸化的激酶.
- 探索RARα和一般转录因子之间的相互作用.
主要方法:
- 局部定向的突变发生能产生S77A RAR突变物.
- 在实验室中使用重组RARα和各种激酶进行酸化试验.
- 在体内联合表达的研究,以评估cdk7对Ser-77酸化和转活的作用.
- 同免疫沉检测RAR与CAK和TFIIH的α结合.
主要成果:
- 突变Ser-77废除了RARαAF-1活动.
- 在体内,CDK7联合表达增强了Ser-77酸化和RARα转活.
- 在体外,自由的CDK激活激酶 (CAK) 和TFIIH酸化的Ser-77均可.
- 稀有阿尔法直接与卡克和TFIIH结合.
结论:
- 通过CDK7的Ser-77酸化对于RARα转活是必不可少的.
- 罕见ARα与通用转录因子TFIIH相互作用.
- 这项研究首次证明了通过通用转录因子的结合和酸化来激活事务激活剂.
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