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目的探讨IκB激酶(IκB kinase,IKK)催化亚基α(IKKα)在紫外线(ultraviolet radiation,UV)诱导的细胞反应中介导p53活化的信号转导机制。方法采用双荧光素酶报告基因分析系统检测在UVB诱导细胞反应中p53的转录激活活性。Western印迹检测IKKα、p53、p38K蛋白表达水平和诱导活化状态。结果 UVB在野生型小鼠成纤维细胞中能显著诱导p53发生磷酸化修饰反应;同时转录激活活性显著提高,IKKα基因敲除后,以上活化反应受到显著抑制,而恢复IKKα表达水平后这种活化反应得以恢复。同样条件下IKKα也能调节p38K的诱导活化,抑制p38K活性显著下调p53的诱导活化水平。结论 IKKα能通过调控p38K活化进而介导UVB诱导p53磷酸化修饰反应。
Objective To investigate the signal transduction mechanism of IκB kinase (IKK) catalytic subunit α (IKKα) which mediates p53 activation in ultraviolet radiation (UV) -induced cell response. Methods Dual luciferase reporter gene assay system was used to detect the transcriptional activation of p53 in UVB-induced cellular responses. Western blotting was used to detect the expression of IKKα, p53, p38K and the induction of activation status. Results UVB induced the phosphorylation of p53 in wild-type mouse fibroblasts. At the same time, the transcriptional activation activity of UVB was significantly increased. After IKKα gene knockdown, the above activation was significantly inhibited, while the activation of IKKα expression was restored The reaction was resumed. Under the same conditions IKKα can also regulate p38K induced activation, inhibition of p38K activity significantly downregulation of p53 induced activation. Conclusion IKKα can mediate UVB-induced phosphorylation of p53 by regulating p38K activation.