细胞周期检测点激酶1的研究进展

Advances in the Research of Checkpoint Kinase 1

细胞周期检测点激酶1(checkpoint kinase 1,Chk1)是一种进化上高度保守的蛋白质激酶,在S期、G_2/M检测点调控细胞周期的进程。受损的DNA可活化Chk1,引起细胞周期阻滞,使受损的DNA得以修复;若损伤广泛而无法修复时则诱导凋亡,从而维持基因组的完整性和稳定性。Chk1缺失的肿瘤细胞表现出多重缺陷,如:细胞增殖缓慢、细胞周期检测点的反应消失、对DNA损伤剂的敏感性增加。由于Chk1的抗损伤作用,Chk1在肿瘤的发生发展、凋亡和耐药机制中起重要作用。

Checkpoint kinase 1(Chkl) is an evolutionarily conserved protein kinase that functions to coordinate cell cycle progression at S phase and G_2/M checkpoint. The activated chkl stops cell cycle transition to facilitate DNA repair in response to DNA damage or triggers apoptosis if the damage is too extensive, which contributes to the maintenance of genomic integrity and stability. Chkl-deficient tumor cells exhibit multiple defects such as slow proliferation, the abrogation of checkpoint response, and an increased sensitivity to the treatment with DNA-damaging agents. Therefore, with its ability to resist stress, Chkl might play an important role in the tumorigenesis, apoptosis and resistance to drugs.