遗传 ›› 2008, Vol. 30 ›› Issue (6): 697-703.doi: 10.3724/SP.J.1005.2008.00697

• 综述 • 上一篇    下一篇

突变体p53研究进展

李大虎;张令强;贺福初   

  1. 军事医学科学院放射与辐射医学研究所, 蛋白质组学国家重点实验室, 北京100850

  • 收稿日期:2008-01-23 修回日期:2008-03-03 出版日期:2008-06-10 发布日期:2008-06-10
  • 通讯作者: 张令强

Advances on mutant p53 research

LI Da-Hu;ZHANG Ling-Qiang;HE Fu-Chu

  

  1. State Key Laboratory of Proteomics, Beijing Institute of Radiation Medicine, Beijing 100850, China
  • Received:2008-01-23 Revised:2008-03-03 Online:2008-06-10 Published:2008-06-10
  • Contact: ZHANG Ling-Qiang

摘要:

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。

关键词: p53, 突变体, 调控机制, 癌症

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 corresponding mutant p53 proteins not only lose wild-type p53 tumor suppressor activities, but also gain new oncogenic properties 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.