令吉明1,2,王 建2,徐晓琳1,耿云峰1,王伟龙1,赵春玲1*,田春艳2*
(1 潍坊医学院山东省高校生物药物重点实验室,潍坊 261000;2 军事科学院军事医学研究院生命组学研究所,国家蛋白质科学中心(北京),北京蛋白质组研究中心,国家蛋白质组学重点实验室,北京 102206)

摘 要:摘 要:p53 作为最重要的抑癌基因之一,在肿瘤的发生发展中起着非常重要的作用。在正常条件下,p53的活性和蛋白水平在细胞内维持着一个较低的水平。当细胞感应应激,p53 发生系列翻译后修饰,蛋白水平和活性发生改变,主要作为转录因子调控多种下游靶基因的表达,从而启动细胞周期阻滞、凋亡、衰老和分化等细胞学效应。p53 的翻译后修饰在响应应激和启动p53 参与相应的细胞学效应的过程中起着重要的作用。p53 的磷酸化修饰是最常见的翻译后修饰,能够影响p53 的稳定性及与反应元件的结合能力,从而调控p53 的活性。现综述p53 的功能结构域,p53 最常见的不同位点的磷酸化修饰及其参与的细胞学效应,并阐释p53 磷酸化在p53 调控中的重要性和与疾病的相关性。

Phosphorylation of p53 and its function
LING Ji-Ming1,2, WANG Jian2, XU Xiao-Lin1, GENG Yun-Feng1,WANG Wei-Long1, ZHAO Chun-Ling1*, TIAN Chun-Yan2*
(1 Key Laboratory of Biological Medicine in Universities of Shangdong Province, Weifang Medical College, Weifang 261000, China; 2 State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China)

Abstract: Abstract: p53, as one of the most famous tumor suppressors, plays a very important role in tumorigenesis and cancer development. Under normal conditions, the activity and protein level of p53 are maintained at low levels in cells. In response to many kinds of stresses, p53 is modified and activated by many kinds of post-translational modifications. The activated p53, mainly as transcription factor, promotes the expression of its downstream target genes, which could trigger cell cycle arrest, apoptosis, senescence, differentiation and so on. Therefore, p53 posttranslational modification is essential to ensure appropriate p53 function. The most common post-translational modification of p53 is phosphorylation. p53 phosphorylation generally results in its stabilization, increases its sequence-specific DNA binding, and then activates p53 selectively. In order to elucidate the important role of phosphorylation on p53 regulation and relevance to disease, in this review, we summarized the functional domain of p53, the important phosphorylation sites of p53 and the related cellular effects.

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