Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, United Kingdom.
FEBS Lett. 2009 Nov 19;583(22):3543-8. doi: 10.1016/j.febslet.2009.09.057. Epub 2009 Oct 13.
The E3 ubiqutin ligase, murne double-minute clone 2 (MDM2), promotes the degradation of p53 under normal homeostatic conditions. Several serine residues within the acidic domain of MDM2 are phosphorylated to maintain its activity but become hypo-phosphorylated following DNA damage, leading to inactivation of MDM2 and induction of p53. However, the signalling pathways that mediate these phosphorylation events are not fully understood. Here we show that the oncogenic and cell cycle-regulatory protein kinase, polo-like kinase-1 (PLK1), phosphorylates MDM2 at one of these residues, Ser260, and stimulates MDM2-mediated turnover of p53. These data are consistent with the idea that deregulation of PLK1 during tumourigenesis may help suppress p53 function.
E3 泛素连接酶、鼠双微基因 2（MDM2）在正常的体内平衡条件下促进 p53 的降解。MDM2 的酸性结构域内的几个丝氨酸残基被磷酸化以保持其活性，但在 DNA 损伤后变得低磷酸化，导致 MDM2 失活和 p53 的诱导。然而，介导这些磷酸化事件的信号通路尚不完全清楚。在这里，我们表明致癌和细胞周期调节蛋白激酶，类 polo 激酶-1（PLK1），在这些残基之一 Ser260 上磷酸化 MDM2，并刺激 MDM2 介导的 p53 周转。这些数据与肿瘤发生过程中 PLK1 的失调可能有助于抑制 p53 功能的观点一致。
