Xpd/Ercc2调节CAK活动和线粒细胞的进展
Jian Chen1, Stéphane Larochelle, Xiaoming Li
1Present address: Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Nature
|July 11, 2003
概括
多菌TFIIH成分Xpd负面调节Cdk7激酶活性,影响细胞循环的进展. 在线粒分裂时的Xpd下调增强了Cdk7的细胞分裂活性,并沉默了转录.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 一般转录因子IIH (TFIIH) 是一个多子单元复合体,对转录和DNA修复至关重要.
- TFIIH含有Cdk激活激酶 (CAK) 亚复合体,包括Cdk7,环林H和MAT1,可激活环林依赖激酶 (Cdks).
- 作为TFIIH的激酶子单元,Cdk7酸化RNA聚合酶II和其他Cdk,调节转录和细胞循环进展.
研究的目的:
- 调查TFIIH组件Xpd在调节Cdk7/CAK活动中的作用.
- 确定Xpd如何影响细胞周期进展和线粒体事件.
- 阐明Xpd,CAK活动和转录调节在线粒分裂过程中的相互作用.
主要方法:
- 利用Drosophila作为一个模型生物.
- 操纵Xpd水平以观察对Cdk7/CAK活性的影响.
- 评估了Cdk T-环酸化,线性进展,细胞增殖和转录活性.
主要成果:
- 过多的Xpd提升了CAK活性,导致Cdk T-循环酸化,线粒细胞缺陷和致死性降低.
- 降低Xpd水平可以增强CAK活性,促进细胞增殖.
- 在线粒分裂开始时,Xpd被下调,这与高Cdk1活性相吻合.
结论:
- 果 Xpd 负面调节 Cdk7/CAK 活性,从而控制细胞循环的进展.
- 在线粒分裂过程中Xpd的下调调节可以调节CAK的活性,从而促进线粒分裂的进展.
- 线粒体对Xpd的下调是抑制细胞分裂期间基底转录的关键机制.
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