突变体p53研究进展幻灯片.pdf

HEREDITAS (Beijing) 2008 6 , 30(6): 697―703 ISSN 0253-9772 综述 DOI: 10.3724/SP.J.1005.2008.00697 p53 李大虎, 张令强, 贺福初 , , 100850 : 抑癌基因突变是癌症发生过程中一个极为关键的事件。p53 作为体内最重要的抑癌基因之一, 在人类癌 症中发生突变的频率高达50%。同时, p53 突变也是人类遗传病Li-Fraumeni 综合征的主要病因。p53 最常见的 突变形式是错义突变, 所形成的突变体p53 不但失去了野生型p53 的抑癌功能, 而且还获得了一系列类似于癌 基因的功能, 促进了肿瘤的进程。文章拟对突变体 p53 的结构功能改变, 获得癌基因活性的分子机制, 以及近 年来对封闭突变体p53 活性所进行的探索等研究方向所取得的进展做一综述。 : p53; 突变体; 癌症; 调控机制 Advances on mutant p53 research LI Da-Hu, ZHANG Ling-Qiang, HE Fu-Chu State Key Laboratory of Proteomics, Beijing Institute of Radiation Medicine, Beijing 100850, China Abstract: Inactivation of tumor suppressor gene is a key event in carcinogenesis. p53 is one of the most important tumor suppressor genes in the genome, and its mutations are found in approximately 50% of human cancers. p53 mutation is also the main cause for human Li-Fraumeni syndrome. The vast majority of p53 mutations are missense mutations, and the cor- responding mutant p53 proteins not only lose wild-type p53 tumor suppressor activities, but also gain new oncogenic prop- erties favoring cancer development. Here, we mainly discussed the structural and functional alterations of mutant p53, the molecular mechanisms underlying gain of oncogenic functions, and the strategies and explorations of suppressing mutant p53 activities. Keywords: p53; mutant; cancer; regulatory mechanism p53 (wtp53) 393 , (Tetramerization domain) 3 ( 1): (1) N , (C-terminal regulatory domain), p53 , DNA SH3 ; (2) , wtp53 DNA (DNA binding domain, DBD), , HDM