Plk3功能链接DNA损伤细胞周期阻滞和细胞凋亡至少部分通过p53通路。
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王谢,吴H, Q, Cogswell JP,侯赛因,康涅狄格州C, Stambrook P,戴Jhanwar-Uniyal M, W
Plk3功能链接DNA损伤细胞周期阻滞和细胞凋亡至少部分通过p53通路。
J生物化学杂志。2001年11月16日,276(46):43305 - 12所示。Epub 2001 9月10。
- PubMed ID
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11551930 (在PubMed]
- 文摘
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Polo-like激酶3(以前称为Plk3 Prk)有助于调节有丝分裂期的细胞周期(欧阳,B。锅,H。陆,L。李,J。Stambrook, P。李,B。戴,w(1997)生物。272年化学,28646 - 28651)。Plk3身体与Cdc25C和磷酸化蛋白质磷酸酶主要在216年丝氨酸(欧阳,B。李,W。锅,H。草地,J。霍夫曼,我。戴,w(1999)致癌基因18,6029 - 6036),表明在有丝分裂Plk3介导的作用,至少在某种程度上,通过Cdc25C的直接监管。在这里,我们表明,异位表达的激酶活性Plk3 (Plk3-A)诱导细胞凋亡。 In response to DNA damage, the kinase activity of Plk3 was rapidly increased in an ATM-dependent manner, whereas that of Plk1 was markedly inhibited. Recombinant Plk3 phosphorylated in vitro a glutathione S-transferase fusion protein containing p53, but not glutathione S-transferase alone. Recombinant Plk1 also phosphorylated p53 but on residues that differed from those targeted by Plk3. Co-immunoprecipitation and pull-down assays demonstrated that Plk3 physically interacted with p53 and that this interaction was enhanced upon DNA damage. In vitro kinase assays followed by immunoblotting showed that serine 20 of p53 was a target of Plk3. Furthermore, expression of a kinase-defective Plk3 mutant (Plk3(K52R)) resulted in significant reduction of p53 phosphorylation on serine 20, which was correlated with a decrease in the expression of p21 and with a concomitant increase in cell proliferation. These results strongly suggest that Plk3 functionally links DNA damage to cell cycle arrest and apoptosis via the p53 pathway.