【摘要】 肿瘤抑制基因p53与其上、下游功能相关基因组成了一个复杂的基因网络。p53基因位于人染色体17q13.1区带,编码的野生型p53蛋白包含N-末端的转录激活结构域、DNA结合结构域、四聚体化结构域和C-末端调节域。p73、p51、p63等基因由于在结构上与p53基因具有同源性,因而被归为p53基因家族。p53是联系不同遗传应急和细胞应答的中间环节,离子辐射、化疗药物及异常的细胞生长信号均能刺激p53基因表达。p53表达升高后,可通过p53-mdm2、p14ARF-mdm2环路对p53表达水平进行精确调节,p53功能的发挥还同时需要p33ING1b基因的协同作用。磷酸化和乙酰化是细胞内调节p53活性功能的主要途径。p53可以调控下游多种基因表达,其功能主要表现在阻滞细胞周期、促进细胞凋亡、维持基因组稳定性和抑制肿瘤血管生成四个方面。认识p53基因网络的功能将有助于理解p53及其相关基因间的具体作用机制。更多还原

【Abstract】 The p53 tumor suppressor gene integrates numerous signals to control cell life and death. p53 and its function related genes consists of a complicated gene network.When a highly connected node in the network breaks down, the disruption of p53 has severe consequences. p53 gene locates in human chromosome 17q13.1. Its encoding wild type p53 protein is composed of four parts: N terminal activation domain, DNA binding domain, oligomerization domain, and C terminal regulation domain. As the gene structures of p73, p51, p63 are similar with p53, they are regarded as members of p53 gene family. p53 play an intermediate role connecting varied stress signals with the reactions of cells. DNA damage caused by ionizing radiation, aberrant growth signals, or chemotherapeutic drugs may activate the p53 network. When expression of p53 elevated, p53 mdm2 and p14ARF mdm2 feedback loops can accurately regulate the expression level of p53, and the cooperation of p33ING1b gene is also needed in the process of p53 exerting normal function. Phosphorylation and acelylation are two important mechanisms to modulate p53 activity in vivo. Several dozen downstream genes are controlled directly by p53, and the activity of p53 falls into four categories: cell cycle inhibition, apoptosis, genetic stability, and inhibition of blood vessel formation. Elucidation of the function of p53 gene network will help to clarify the interaction mechanisms of p53 gene and its function related genes.更多还原