Li Da-Hu, Zhang Ling-Qiang, He Fu-Chu
State Key Laboratory of Proteomics, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Yi Chuan. 2008 Jun;30(6):697-703. doi: 10.3724/sp.j.1005.2008.00697.
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.
肿瘤抑制基因的失活是致癌过程中的关键事件。p53是基因组中最重要的肿瘤抑制基因之一,在大约50%的人类癌症中都发现有其突变。p53突变也是人类李-佛美尼综合征的主要病因。绝大多数p53突变是错义突变,相应的突变型p53蛋白不仅丧失野生型p53的肿瘤抑制活性,还获得了有利于癌症发展的新致癌特性。在此,我们主要讨论了突变型p53的结构和功能改变、致癌功能获得的分子机制,以及抑制突变型p53活性的策略和探索。