Cdc25-dependent activation of cyclin A/cdk2 is blocked in G2 phase arrested cells independently of ATM/ATR
Cdc25-dependent activation of cyclin A/cdk2 is blocked in G2 phase arrested cells independently of ATM/ATR
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DOI：
10.1038/sj.onc.1204177
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发表时间：
2001-02-22
期刊：
影响因子：
8
通讯作者：
Gabrielli, B
中科院分区：
文献类型：
--
作者：
Goldstone, S;Pavey, S;Gabrielli, B
Cyclin A/cdk 2在细胞周期的S期和G2期有活性，但其在G2期的调节和功能知之甚少。在这项研究中，我们研究了调节细胞周期蛋白A/cdk 2活性在正常的G2期进展和遗传毒素诱导的G2期阻滞。我们发现，细胞周期蛋白A/cdk 2被激活，在早期G2期的cdc 25活动。在响应于各种形式的DNA损伤而启动的G2期检查点阻滞中，细胞周期蛋白A/cdk 2和细胞周期蛋白B1/cdc 2的cdc 25依赖性激活被阻断。在G2期阻滞的细胞中，cdc 25 B的异位表达有效地激活了细胞周期蛋白A/cdk 2和细胞周期蛋白B1/cdc 2，而不是cdc 25 C。最后，我们证明了在G2检查点阻滞中细胞周期蛋白A/cdk 2激活的阻断与ATM/ATR无关。我们推测，ATM/ATR非依赖性阻断G2期细胞周期蛋白A/cdk 2的激活可能作为检查点控制的进一步层，并且阻断G2期细胞周期蛋白A/cdk 2的激活有助于G2期检查点阻滞。
Cyclin A/cdk2 is active during S and G2 phases of the cell cycle, but its regulation and function during G2 phase is poorly understood. In this study we have examined the regulation of cyclin A/cdk2 activity during normal G2 phase progression and in genotoxin-induced G2 arrest. We show that cyclin A/cdk2 is activated in early G2 phase by a cdc25 activity. In the G2 phase checkpoint arrest initiated in response to various forms of DNA damage, the cdc25-dependent activation of both cyclin A/cdk2 and cyclin B1/cdc2 is blocked. Ectopic expression of cdc25B, but not cdc25C, in G2 phase arrested cells efficiently activated both cyclin A/cdk2 and cyclin B1/cdc2. Finally, we demonstrate that the block in cyclin A/cdk2 activation in the G2 checkpoint arrest is independent of ATM/ATR. We speculate that the ATM/ ATR-independent block in G2 phase cyclin A/cdk2 activation may act as a further layer of checkpoint control, and that blocking G2 phase cyclin A/cdk2 activation contributes to the G2 phase checkpoint arrest.