Goto Hidemasa, Kasahara Kousuke, Inagaki Masaki
Division of Biochemistry, Aichi Cancer Center Research Institute; Department of Cellular Oncology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
Cell Struct Funct. 2015;40(1):43-50. doi: 10.1247/csf.14017. Epub 2014 Dec 25.
Checkpoint kinase 1 (Chk1) is a conserved protein kinase central to the cell-cycle checkpoint during DNA damage response (DDR). Until recently, ATR, a protein kinase activated in response to DNA damage or stalled replication, has been considered as the sole regulator of Chk1. Recent progress, however, has led to the identification of additional protein kinases involved in Chk1 phosphorylation, affecting the subcellular localization and binding partners of Chk1. In fact, spatio-temporal regulation of Chk1 is of critical importance not only in the DDR but also in normal cell-cycle progression. In due course, many potent inhibitors targeted to Chk1 have been developed as anticancer agents and some of these inhibitors are currently in clinical trials. In this review, we summarize the current knowledge of Chk1 regulation by phosphorylation.
检查点激酶1（Chk1）是一种保守的蛋白激酶，在DNA损伤反应（DDR）期间的细胞周期检查点中起着核心作用。直到最近，ATR作为一种响应DNA损伤或复制停滞而被激活的蛋白激酶，一直被认为是Chk1的唯一调节因子。然而，最近的进展导致了其他参与Chk1磷酸化的蛋白激酶的鉴定，这些激酶影响Chk1的亚细胞定位和结合伙伴。事实上，Chk1的时空调节不仅在DDR中至关重要，在正常细胞周期进程中也同样重要。随着时间的推移，许多靶向Chk1的强效抑制剂已被开发为抗癌药物，其中一些抑制剂目前正在进行临床试验。在这篇综述中，我们总结了目前关于Chk1磷酸化调节的知识。
