p53修饰及其相互作用的研究进展

Advances in interaction of p53 postranslational modifications

p53是一个重要的抑癌分子,在抑制肿瘤发生发展过程中起关键作用.正常生理状况下,p53水平很低,细胞受到外界刺激后,p53水平升高,稳定性增强,继而参与细胞周期阻滞、细胞衰老、DNA修复或细胞凋亡等重要的生命过程.p53功能的精确调控至关重要,涉及一系列翻译后修饰(泛素化、乙酰化、磷酸化、甲基化、泛素样蛋白质修饰等等),这些作用互相协作、相互影响,从而精密调节p53的活性.本文探讨p53的各种修饰作用,并分析其各种修饰与肿瘤发生的相互关系,为肿瘤的治疗提供一些参考价值.

p53, as a tumor suppressor, plays a critical role in inhibiting development of cancer. Generally, p53 sustains a constant low level in cells at physiological conditions, however, p53 is significantly increased in response to various stresses, through which regulates cell cycle arrest, senescence, DNA damage repair and apoptosis. Functional modifications of p53 involve a series of posttranslational modifications including ubiquitination, acetylation, phosphorylation, sumolation/ neddylation and methylation. These modifications interact each other and thus mutually regulate p53 activities. This review focuses on interactions of various posttranslational modifications of p53, and tries to provide a potential strategy for clinical cancer therapeutics.