Polo-like kinase 1 对 G2 和 S 期表达的 1 蛋白的磷酸化对于 G2 检查点恢复过程中 p53 的失活至关重要。
Polo-like kinase 1 phosphorylation of G2 and S-phase-expressed 1 protein is essential for p53 inactivation during G2 checkpoint recovery.
机构信息
Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907, USA.
出版信息
EMBO Rep. 2010 Aug;11(8):626-32. doi: 10.1038/embor.2010.90. Epub 2010 Jun 25.
Abstract
In response to G2 DNA damage, the p53 pathway is activated to lead to cell-cycle arrest, but how p53 is eliminated during the subsequent recovery process is poorly understood. It has been established that Polo-like kinase 1 (Plk1) controls G2 DNA-damage recovery. However, whether Plk1 activity contributes to p53 inactivation during this process is unknown. In this study, we show that G2 and S-phase-expressed 1 (GTSE1) protein, a negative regulator of p53, is required for G2 checkpoint recovery and that Plk1 phosphorylation of GTSE1 at Ser 435 promotes its nuclear localization, and thus shuttles p53 out of the nucleus to lead to its degradation during the recovery.
摘要
针对 G2 期 DNA 损伤，p53 通路被激活以导致细胞周期停滞，但在随后的恢复过程中 p53 是如何被清除的尚不清楚。已经证实，Polo 样激酶 1（Plk1）控制 G2 期 DNA 损伤的恢复。然而，在这个过程中 Plk1 的活性是否有助于 p53 的失活尚不清楚。在这项研究中，我们表明，G2 和 S 期表达的 1（GTSE1）蛋白是 p53 的负调控因子，对于 G2 期检查点恢复是必需的，而且 Plk1 对 GTSE1 丝氨酸 435 的磷酸化促进其核定位，从而将 p53 从核内转位出去，导致其在恢复过程中降解。
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