p21Cip1/WAF1 mediates cyclin B1 degradation in response to DNA damage
p21Cip1/WAF1 mediates cyclin B1 degradation in response to DNA damage
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DOI：
10.4161/cc.8.2.7550
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发表时间：
2009-01-15
期刊：
影响因子：
4.3
通讯作者：
Lee, Patrick W. K.
中科院分区：
文献类型：
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作者：
Gillis, Laura D.;Leidal, Andrew M.;Lee, Patrick W. K.
p21（Cip1/WAF1）是响应DNA损伤的细胞周期阻滞的主要介质。p21主要通过灭活G(1)相关的细胞周期蛋白a和含有细胞周期蛋白e的细胞周期蛋白/cdk复合物，介导G(1)细胞周期阻滞。在本研究中，我们研究了p21在DNA损伤诱导的G(2)细胞周期阻滞中的作用，特别是关于G(2)相关的细胞周期蛋白，细胞周期蛋白B1。我们证明，与野生型细胞相比，缺乏p21或缺乏上调p21能力的细胞在DNA损伤时无法介导细胞周期蛋白B1的下调。在野生型细胞中，DNA损伤导致细胞周期蛋白B1水平下降，这是由于p21介导的细胞周期蛋白B1降解，这可以被蛋白酶体抑制剂抑制。细胞周期分析表明，p21-null细胞不能维持G(2)细胞周期阻滞，并在DNA含量大于4N时积累。这些结果表明，p21介导的细胞周期蛋白B1对DNA损伤的降解对于维持G(2)细胞周期阻滞是必要的。
p21(Cip1/WAF1) is the principle mediator of cell cycle arrest in response to DNA damage. p21 primarily mediates G(1) cell cycle arrest by inactivating G(1)-associated cyclin A-and cyclin E-containing cyclin/cdk complexes. In the present study we investigate the role of p21 in DNA damage-induced G(2) cell cycle arrest, particularly with respect to the G(2)-associated cyclin, cyclin B1. We demonstrate that cells lacking p21 or deficient in their ability to upregulate p21 are unable to mediate the downregulation of cyclin B1 in response to DNA damage as compared to wild-type cells. Decreased levels of cyclin B1 in response to DNA damage seen in wild-type cells is due to p21-mediated degradation of cyclin B1 as this can be inhibited by a proteasomal inhibitor. Cell cycle analysis reveals that p21-null cells are unable sustain G(2) cell cycle arrest and accumulate at greater than 4N DNA content. These results indicate that p21-mediated degradation of cyclin B1 in response to DNA damage is necessary for the maintenance of G(2) cell cycle arrest.