Innocente S A, Abrahamson J L, Cogswell J P, Lee J M
Hamilton Regional Cancer Center, 699 Concession Street, Hamilton, Ontario, Canada L8V 5C2.
Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2147-52. doi: 10.1073/pnas.96.5.2147.
The p53 tumor suppressor controls multiple cell cycle checkpoints regulating the mammalian response to DNA damage. To identify the mechanism by which p53 regulates G2, we have derived a human ovarian cell that undergoes p53-dependent G2 arrest at 32 degrees C. We have found that p53 prevents G2/M transition by decreasing intracellular levels of cyclin B1 protein and attenuating the activity of the cyclin B1 promoter. Cyclin B1 is the regulatory subunit of the cdc2 kinase and is a protein required for mitotic initiation. The ability of p53 to control mitotic initiation by regulating intracellular cyclin B1 levels suggests that the cyclin B-dependent G2 checkpoint has a role in preventing neoplastic transformation.
p53肿瘤抑制因子控制多个细胞周期检查点,调节哺乳动物对DNA损伤的反应。为了确定p53调节G2期的机制,我们培育出了一种人卵巢细胞,该细胞在32摄氏度时会发生p53依赖的G2期阻滞。我们发现,p53通过降低细胞周期蛋白B1的细胞内水平并减弱细胞周期蛋白B1启动子的活性来阻止G2/M期转换。细胞周期蛋白B1是cdc2激酶的调节亚基,是有丝分裂起始所需的一种蛋白质。p53通过调节细胞内细胞周期蛋白B1水平来控制有丝分裂起始的能力表明,依赖细胞周期蛋白B的G2期检查点在预防肿瘤转化中发挥作用。