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预虫BID是DNA损伤反应中的ATM效应因子
Iris Kamer1, Rachel Sarig, Yehudit Zaltsman
1Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
Cell
|August 27, 2005
概括
仅BH3蛋白BID对于DNA损伤后的细胞亡和细胞循环停止至关重要. 它通过ATM激酶的酸化对这些过程至关重要,这表明它在细胞死亡和存活中起着双重作用.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 只有BH3的蛋白质,如BID,是细胞亡的关键调节者.
- DNA 损伤会触发细胞反应,包括细胞循环停止和细胞亡.
研究的目的:
- 研究BID蛋白在DNA损伤诱导的亡和细胞周期调节中的作用.
- 为了阐明在DNA双链断裂后BID酸化的机制.
主要方法:
- BID.的细胞局部化研究.
- 在对DNA损伤的反应中对BID酸化的分析.
- 在细胞周期停止试验中使用BID淘汰细胞和BID突变体.
- 使用埃托波西德 (etoposide) 进行治疗,它是一种拓聚酶II的毒素.
主要成果:
- 在健康细胞中,BID部分局限于细胞核.
- 在DNA双链断裂后,BID在两个共识位点被ATM激酶酸化.
- 在乙托化物治疗后,BID淘汰细胞未能在S阶段被捕.
- 野生型BID的恢复挽救了S阶段的停止,但非酸化BID突变物没有.
结论:
- BID是对DNA损伤的反应中ATM激酶的作用因子.
- 在S阶段停止过程中,BID酸化是必不可少的.
- 预位性BID也可能在DNA损伤反应中起到生存作用.
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