Menendez D, Inga A, Jordan J J, Resnick M A
Laboratory of Molecular Genetics, Chromosome Stability Section, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA.
Oncogene. 2007 Apr 2;26(15):2191-201. doi: 10.1038/sj.onc.1210277.
The p53 master regulatory network provides for the stress-responsive direct control of a vast number of genes in humans that can be grouped into several biological categories including cell-cycle control, apoptosis and DNA repair. Similar to other sequence-specific master regulators, there is a matrix of key components, which provide for variation within the p53 master regulatory network that include p53 itself, target response element sequences (REs) that provide for p53 regulation of target genes, chromatin, accessory proteins and transcription machinery. Changes in any of these can impact the expression of individual genes, groups of genes and the eventual biological responses. The many REs represent the core of the master regulatory network. Since defects or altered expression of p53 are associated with over 50% of all cancers and greater than 90% of p53 mutations are in the sequence-specific DNA-binding domain, it is important to understand the relationship between wild-type or mutant p53 proteins and the target response elements. In the words of the legendary detective Sherlock Holmes, it is 'Elementary, my dear Mr. Watson'.
p53主调控网络可对人类大量基因进行应激反应直接调控，这些基因可分为几个生物学类别，包括细胞周期控制、细胞凋亡和DNA修复。与其他序列特异性主调控因子类似，存在一个关键成分矩阵，这使得p53主调控网络存在变异，其中包括p53自身、提供p53对靶基因调控的靶反应元件序列（REs）、染色质、辅助蛋白和转录机制。这些成分中任何一个发生变化都可能影响单个基因、基因群的表达以及最终的生物学反应。众多的REs代表了主调控网络的核心。由于p53的缺陷或表达改变与超过50%的所有癌症相关，且超过90%的p53突变位于序列特异性DNA结合结构域，因此了解野生型或突变型p53蛋白与靶反应元件之间的关系很重要。用传奇侦探夏洛克·福尔摩斯的话说，就是“这很简单，我亲爱的华生先生”。
