Hupp T R, Lane D P, Ball K L
Cancer Research Campaign Laboratories, Department of Molecular and Cellular Pathology, University of Dundee Medical School, Dundee DD1 9SY, Scotland, UK.
Biochem J. 2000 Nov 15;352 Pt 1(Pt 1):1-17.
Human cancer progression is driven in part by the mutation of oncogenes and tumour-suppressor genes which, under selective environmental pressures, give rise to evolving populations of biochemically altered cells with enhanced tumorigenic and metastatic potential. Given that human cancers are biologically and pathologically quite distinct, it has been quite surprising that a common event, perturbation of the p53 pathway, occurs in most if not all types of human cancers. The central role of p53 as a tumour-suppressor protein has fuelled interest in defining its mechanism of function and regulation, determining how its inactivation facilitates cancer progression, and exploring the possibility of restoring p53 function for therapeutic benefit. This review will highlight the key biochemical properties of p53 protein that affect its tumour-suppressor function and the experimental strategies that have been developed for the re-activation of the p53 pathway in cancers.
人类癌症进展部分是由癌基因和肿瘤抑制基因的突变驱动的，在选择性环境压力下，这些基因会产生具有不断增强的致瘤和转移潜能的生物化学改变细胞群体。鉴于人类癌症在生物学和病理学上有很大差异，一个常见事件——p53通路的扰动，在大多数（如果不是所有）人类癌症类型中发生，这一点相当令人惊讶。p53作为一种肿瘤抑制蛋白的核心作用激发了人们对确定其功能和调控机制、确定其失活如何促进癌症进展以及探索恢复p53功能以获得治疗益处的可能性的兴趣。本综述将重点介绍影响p53蛋白肿瘤抑制功能的关键生化特性，以及为在癌症中重新激活p53通路而开发的实验策略。
