Chen Jie, Dai Gu, Wang Yi-Qian, Wang Sheng, Pan Fei-Yan, Xue Bin, Zhao Dong-Hong, Li Chao-Jun
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, Life Sciences College, Nanjing Normal University, Nanjing 210097, China.
FEBS Lett. 2006 Jun 26;580(15):3624-30. doi: 10.1016/j.febslet.2006.05.047. Epub 2006 May 30.
Ultraviolet (UV) irradiation can result in cell cycle arrest. The reactivation of Polo-like kinase 1 (Plk1) is necessary for cell cycle reentry. But the mechanism of how Plk1 regulates p53 in UV-induced mitotic arrest cells remained elusive. Here we find that UV treatment leads HEK293 cells to inverse changes of Plk1 and p53. Over-expression of Plk1 rescue UV-induced mitotic arrest cells by inhibiting p53 activation. Plk1 could also inhibit p53 phosphorylation at Ser15, thus facilitates its nuclear export and degradation. Further examination shows that Plk1, p53 and Cdc25C can form a large complex. Plk1 could bind to the sequence-specific DNA-binding domain of p53 and active Cdc25C by hyperphosphorylation. These results hypothesize that Plk1 and Cdc25C participate in recovery the mitotic arrest through binding to the different domain of p53. Cdc25C may first be actived by Plk1, and then its phosphatase activity makes p53 dephosphorylated at Ser15.
紫外线（UV）照射可导致细胞周期停滞。Polo样激酶1（Plk1）的重新激活是细胞周期重新进入所必需的。但在紫外线诱导的有丝分裂停滞细胞中，Plk1如何调节p53的机制仍不清楚。在此，我们发现紫外线处理导致HEK293细胞中Plk1和p53发生相反变化。Plk1的过表达通过抑制p53激活来挽救紫外线诱导的有丝分裂停滞细胞。Plk1还可抑制p53在Ser15位点的磷酸化，从而促进其核输出和降解。进一步研究表明，Plk1、p53和Cdc25C可形成一个大复合物。Plk1可与p53的序列特异性DNA结合结构域结合，并通过过度磷酸化激活Cdc25C。这些结果推测，Plk1和Cdc25C通过与p53的不同结构域结合参与有丝分裂停滞的恢复。Cdc25C可能首先被Plk1激活，然后其磷酸酶活性使p53在Ser15位点去磷酸化。
