Lu Si-Qian, Jia Shu-Ting, Luo Ying
Lab of Molecular Genetics of Aging and Tumor, Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650224, China.
Yi Chuan. 2011 Jun;33(6):539-48. doi: 10.3724/sp.j.1005.2011.00539.
Protein p53 is the most intensively studied tumor suppressor protein. Recent studies keep revealing its new function in metabolism and reproduction. At the same time, it is also found that varieties of p53 mutant gained new function in promoting tumorigenesis. These studies provide the basis for understanding the personalized gain of function of p53 mu-tants and help us searching for the new strategies for reactivation of wild-type p53 and correction of the function of p53 mutants. The personalized treatment targeting different p53 mutants will be the focus for cancer treatment. Here, we re-viewed the discovered gain of function of some p53 mutants and the molecular strategies for reactivating wild type p53 function: by use of small molecules or polypeptides to reactivate the wild type function of p53 mutants in tumor cells; by exogenous expression of wild type p53 carried by recombinant adenovirus in tumor cells; and by inhibition the interaction between p53 and mdm2 to stabilize wild type p53 proteins. Further study of variety of p53 point mutations farcilitates de-signing more effectively personalized strategies in the cancer therapy.
蛋白质p53是研究最为深入的肿瘤抑制蛋白。近期研究不断揭示其在代谢和生殖方面的新功能。与此同时,还发现多种p53突变体在促进肿瘤发生方面获得了新功能。这些研究为理解p53突变体的个性化功能获得提供了基础,并有助于我们寻找重新激活野生型p53以及纠正p53突变体功能的新策略。针对不同p53突变体的个性化治疗将成为癌症治疗的重点。在此,我们回顾了一些p53突变体已发现的功能获得情况以及重新激活野生型p53功能的分子策略:利用小分子或多肽在肿瘤细胞中重新激活p53突变体的野生型功能;通过重组腺病毒携带野生型p53在肿瘤细胞中外源表达;以及通过抑制p53与mdm2之间的相互作用来稳定野生型p53蛋白。对多种p53点突变的进一步研究有助于在癌症治疗中设计出更有效的个性化策略。