细胞分裂周期蛋白6:新的抗肿瘤靶点

Cell Cycle Division 6:New Anticancer Target

真核细胞中细胞分裂周期蛋白6(cell division cycle 6,Cdc6)是起始细胞DNA复制的必需蛋白,其主要功能是参与组装完成"复制前复合体(pre-replication complexes,pre-RC)"。近期的研究发现,Cdc6在调控细胞有丝分裂方面也具有重要作用。Cdc6介导基因组异常情况下ATR监测点信号的活化,从而阻止有丝分裂的提前进入。Cdc6还可抑制有丝分裂期CDK1的活性,促进有丝分裂滑脱。因此,Cdc6必然与细胞的恶性增殖及恶性转化密切相关,抑制Cdc6将会产生有效的抗肿瘤作用。该文总结了近年来的研究成果,阐述了Cdc6在肿瘤发生发展中的作用,重点讨论了Cdc6在调控有丝分裂中的作用,以及抑制Cdc6在抗肿瘤中的作用。

Cell division cycle 6 （Cdc6） is an essential regulator of DNA replication in eukaryotic cells. Its best-characterized function is the assembly of pre-replication complexes （pre-RC）. Recent studies have shown that Cdc6 also participates in the regulation of mitosis. Cdc6 can inhibit pre-mature mitotic entry under replication stress by mediating the ATR checkpoint activation. In addition, Cdc6 can promote mitotic slippage by inhibiting mitotic CDK1 activity. Therefore, as a tumor-highly-related protein, Cdc6 promotes cell proliferation and malignant transformation. Cdc6 function disturbance could elicit potent anticancer effects. In this review, we summarized the relations of Cdc6 function with tumor malignant progress, emphasizing on the mitosis regulation of Cdc6 and the possible anticancer activity by Cdc6 targeting.