Institute for Cancer Genetics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
J Mol Cell Biol. 2019 Jul 19;11(7):564-577. doi: 10.1093/jmcb/mjz060.
The last 40 years have witnessed how p53 rose from a viral binding protein to a central factor in both stress responses and tumor suppression. The exquisite regulation of p53 functions is of vital importance for cell fate decisions. Among the multiple layers of mechanisms controlling p53 function, posttranslational modifications (PTMs) represent an efficient and precise way. Major p53 PTMs include phosphorylation, ubiquitination, acetylation, and methylation. Meanwhile, other PTMs like sumoylation, neddylation, O-GlcNAcylation, adenosine diphosphate (ADP)-ribosylation, hydroxylation, and β-hydroxybutyrylation are also shown to play various roles in p53 regulation. By independent action or interaction, PTMs affect p53 stability, conformation, localization, and binding partners. Deregulation of the PTM-related pathway is among the major causes of p53-associated developmental disorders or diseases, especially in cancers. This review focuses on the roles of different p53 modification types and shows how these modifications are orchestrated to produce various outcomes by modulating p53 activities or targeted to treat different diseases caused by p53 dysregulation.
过去的 40 年见证了 p53 如何从一种病毒结合蛋白上升为应激反应和肿瘤抑制的核心因素。p53 功能的精细调节对于细胞命运决策至关重要。在控制 p53 功能的多种机制中，翻译后修饰 (PTM) 是一种有效且精确的方式。p53 的主要 PTM 包括磷酸化、泛素化、乙酰化和甲基化。同时，其他 PTM，如 SUMOylation、NEDDylation、O-GlcNAcylation、二磷酸腺苷 (ADP)-核糖基化、羟基化和 β-羟基丁酰化，也被证明在 p53 调节中发挥各种作用。通过独立作用或相互作用，PTM 影响 p53 的稳定性、构象、定位和结合伙伴。PTM 相关途径的失调是 p53 相关发育障碍或疾病（尤其是癌症）的主要原因之一。本综述重点介绍了不同 p53 修饰类型的作用，并展示了这些修饰如何通过调节 p53 活性或针对由 p53 失调引起的不同疾病进行靶向治疗来协调产生各种结果。
