State Key Laboratory of Medical Molecular Biology & Department of Medical Genetics, Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
J Mol Cell Biol. 2022 Jan 21;13(11):774-785. doi: 10.1093/jmcb/mjab047.
The genome guardian p53 functions as a transcription factor that senses numerous cellular stresses and orchestrates the corresponding transcriptional events involved in determining various cellular outcomes, including cell cycle arrest, apoptosis, senescence, DNA repair, and metabolic regulation. In response to diverse stresses, p53 undergoes multiple posttranslational modifications (PTMs) that coordinate with intimate interdependencies to precisely modulate its diverse properties in given biological contexts. Notably, PTMs can recruit 'reader' proteins that exclusively recognize specific modifications and facilitate the functional readout of p53. Targeting PTM-reader interplay has been developing into a promising cancer therapeutic strategy. In this review, we summarize the advances in deciphering the 'PTM codes' of p53, focusing particularly on the mechanisms by which the specific reader proteins functionally decipher the information harbored within these PTMs of p53. We also highlight the potential applications of intervention with p53 PTM-reader interactions in cancer therapy and discuss perspectives on the 'PTMomic' study of p53 and other proteins.
基因组守护者 p53 作为一种转录因子发挥作用，能够感知多种细胞应激，并协调参与决定各种细胞结果的相应转录事件，包括细胞周期停滞、细胞凋亡、衰老、DNA 修复和代谢调节。p53 会发生多种翻译后修饰（PTM），这些修饰协同作用，在特定的生物学背景下精确调节其多种特性。值得注意的是，PTM 可以招募“读取器”蛋白，这些蛋白专门识别特定的修饰，并促进 p53 的功能读取。靶向 PTM-读取器相互作用已成为一种很有前途的癌症治疗策略。在这篇综述中，我们总结了破译 p53“PTM 密码”的进展，特别关注特定的读取器蛋白如何在功能上破译 p53 中这些 PTM 所包含的信息的机制。我们还强调了干预 p53 PTM-读取器相互作用在癌症治疗中的潜在应用，并讨论了对 p53 和其他蛋白质的“PTM 组学”研究的观点。
