p53 regulates a G2 checkpoint through cyclin B1

p53 regulates a G2 checkpoint through cyclin B1
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DOI:
10.1073/pnas.96.5.2147
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发表时间:
1999-03-02
影响因子:
11.1
通讯作者:
Lee, JM
Lee, JM
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Innocente, SA;Abrahamson, JLA;Lee, JM

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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G(2)的机制,我们获得了在32 ℃经历p53依赖性G(2)停滞的人卵巢细胞。我们发现p53通过降低细胞内cyclin B1蛋白水平和减弱cyclin B1启动子的活性来阻止G(2)/M转换。细胞周期蛋白B1是cdc 2激酶的调节亚基,是有丝分裂起始所需的蛋白质。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细胞周期蛋白B依赖的G(2)检查点在预防肿瘤转化中起作用。
The p53 tumor suppressor controls multiple cell cycle checkpoints regulating the mammalian response to DNA damage. To identify the mechanism by which p53 regulates G(2), we have derived a human ovarian cell that undergoes p53-dependent G(2) arrest at 32 degrees C. We have found that p53 prevents G(2)/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 G(2) checkpoint has a role in preventing neoplastic transformation.