Chen Yue, Poon Randy Y C
Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong.
Front Biosci. 2008 May 1;13:5016-29. doi: 10.2741/3060.
Cell cycle checkpoints are pivotal mechanisms safeguarding genome stability. Cells that harbor defects in checkpoints are predisposed to genome instability and neoplastic transformation. Two structurally-unrelated protein kinases, CHK1 and CHK2, are implicated in several major checkpoints of the cell cycle, providing a crucial linkage between the upstream sensors of the checkpoints and the cell cycle engine. Variations of the ATM/ATR-CHK1/CHK2-CDC25-CDK axis underlie the molecular basis of the replication checkpoint, the intra-S phase checkpoint, and the G2 DNA damage checkpoint. Although some aspects of the pathway remain contentious, the ATM/ATR-CHK1/CHK2-p53-p21CIP1/WAF1-CDK axis is believed to play an important role in the G1 DNA damage checkpoint. Recent data also reveal that CHK1 may play a role in the spindle-assembly checkpoint. Finally, CHK1 and CHK2 are implicated in linking the cell cycle to diverse processes such as senescence and the circadian cycle. In this review article, we provide an overview of how the multi-tasking nature of CHK1 and CHK2 is achieved in vertebrate cells.
细胞周期检查点是保障基因组稳定性的关键机制。在检查点存在缺陷的细胞易于发生基因组不稳定和肿瘤转化。两种结构不相关的蛋白激酶CHK1和CHK2参与细胞周期的几个主要检查点，在检查点的上游传感器与细胞周期引擎之间提供关键联系。ATM/ATR-CHK1/CHK2-CDC25-CDK轴的变化是复制检查点、S期内检查点和G2期DNA损伤检查点的分子基础。尽管该途径的某些方面仍存在争议，但ATM/ATR-CHK1/CHK2-p53-p21CIP1/WAF1-CDK轴被认为在G1期DNA损伤检查点中起重要作用。最近的数据还表明，CHK1可能在纺锤体组装检查点中发挥作用。最后，CHK1和CHK2参与将细胞周期与衰老和昼夜节律等多种过程联系起来。在这篇综述文章中，我们概述了脊椎动物细胞中CHK1和CHK2的多任务特性是如何实现的。
