Chumakov P M
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.
Biochemistry (Mosc). 2007 Dec;72(13):1399-421. doi: 10.1134/s0006297907130019.
The p53 tumor suppressor plays a pivotal role in multicellular organism by enforcing benefits of the organism over those of an individual cell. The task of p53 is to control the integrity and correctness of all processes in each individual cell and in the organism as a whole. Information about the state of ongoing events in the cell is gathered through multiple signaling pathways that convey signals modifying activities of p53. Changes in the activities depend on the character of damages or deviations from optimum in processes, and the activity of p53 changes depending on the degree of the aberration, which results in either stimulation of repair processes and protective mechanisms, or the cessation of further cell divisions and the induction of programmed cell death. The strategy of p53 ensures genetic identity of cells and prevents the selection of abnormal cells. By accomplishing these strategic tasks, p53 may use a wide spectrum of activities, such as its ability to function as a transcription factor, by inducing or repressing different genes, or as an enzyme, by acting as an exonuclease during DNA reparation, or as an adaptor or a regulatory protein, intervening into functions of numerous signaling pathways. Loss of function of the p53 gene occurs in virtually every case of cancer, and deficiency in p53 is an unavoidable prerequisite to the development of malignancies. The functions of p53 play substantial roles in many other pathologies as well as in the aging process. This review is focused on strategies of the p53 gene, demonstrating individual mechanisms underlying its functions.
p53肿瘤抑制因子在多细胞生物体中发挥着关键作用，它强化生物体整体利益而非单个细胞的利益。p53的任务是控制每个单个细胞以及整个生物体中所有过程的完整性和正确性。细胞中正在进行的事件状态信息通过多种信号通路收集，这些信号通路传递修饰p53活性的信号。活性变化取决于过程中损伤的性质或与最佳状态的偏差，p53的活性根据异常程度而变化，这会导致修复过程和保护机制的激活，或者进一步细胞分裂的停止以及程序性细胞死亡的诱导。p53的策略确保细胞的基因一致性并防止异常细胞的选择。通过完成这些战略任务，p53可以利用广泛的活性，例如作为转录因子，通过诱导或抑制不同基因发挥作用；作为酶，在DNA修复过程中作为核酸外切酶发挥作用；或者作为衔接子或调节蛋白，干预众多信号通路的功能。p53基因功能丧失几乎出现在每一例癌症中，p53缺陷是恶性肿瘤发生不可避免的先决条件。p53的功能在许多其他病理过程以及衰老过程中也发挥着重要作用。本综述聚焦于p53基因的策略，阐述其功能背后的个体机制。
