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Requirement for tyrosine phosphorylation of Cdk4 in G1 arrest induced by ultraviolet irradiation.

机译:Cdk4的酪氨酸磷酸化对由紫外线照射引起的G1阻滞的要求。

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摘要

Exposure to ultraviolet light arrests the function of mammalian fibroblasts in the G1 phase of the cell cycle, as well as the S and G2 phases. Although p21, an inhibitor of cyclin-dependent kinase (Cdk) that is induced by DNA damage may partly account for the arrest in G1 (ref. 1), the mechanism is little understood. Here we show that tyrosine phosphorylation of Cdk4 is required for this arrest. In rat fibroblast, Cdk4 is tyrosine-phosphorylated during G1 progression, and its dephosphorylation is required for S phase. When cells are ultraviolet-irradiated, their arrest in G1 is accompanied by an increase in phosphorylation level. Conversely, cells expressing unphosphorylatable Cdk4F17 fail to arrest in G1, and suffer significantly elevated chromosomal aberrations and cell death.
机译:暴露于紫外线下会在细胞周期的G1期以及S和G2期阻止哺乳动物成纤维细胞的功能。尽管p21是一种由DNA损伤诱导的细胞周期蛋白依赖性激酶(Cdk)抑制剂,可能部分解释了G1的阻滞作用(参考文献1),但其机理尚不清楚。在这里,我们显示Cdk4的酪氨酸磷酸化是此逮捕所需的。在大鼠成纤维细胞中,Cdk4在G1进程中被酪氨酸磷酸化,S期需要其去磷酸化。当细胞受到紫外线照射时,它们在G1中的滞留伴随着磷酸化水平的提高。相反,表达不可磷酸化的Cdk4F17的细胞无法在G1中停滞,并显着升高的染色体畸变和细胞死亡。

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