Polo-like kinase 1 regulates mitotic arrest after UV irradiation through dephosphorylation of p53 and inducing p53 degradation.
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.
Chen
Jie
J
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, Life Sciences College, Nanjing Normal University, Nanjing 210097, China.
Dai
Gu
G
Wang
Yi-Qian
YQ
Wang
Sheng
S
Pan
Fei-Yan
FY
Xue
Bin
B
Zhao
Dong-Hong
DH
Li
Chao-Jun
CJ
D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004249:DNA Damage / Q000235:genetics; D006801:Humans; D008938:Mitosis / Q000528:radiation effects*; D010766:Phosphorylation / Q000528:radiation effects; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D020687:cdc25 Phosphatases / Q000378:metabolism; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D010768:Phosphoserine; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D020687:cdc25 Phosphatases; D000097869:Polo-Like Kinase 1; C517009:CDC25C protein, human