Abstract

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.

中文翻译：

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破译肿瘤抑制基因 p53 的 PTM 代码

摘要

基因组守护者 p53 作为一种转录因子发挥作用，可感知众多细胞压力并协调参与确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。为了应对不同的压力，p53 经历了多种翻译后修饰 (PTM)，这些修饰与密切的相互依赖性相协调，以在给定的生物学环境中精确调节其不同的特性。值得注意的是，翻译后修饰可以招募专门识别特定修饰并促进 p53 功能读出的“阅读器”蛋白质。针对 PTM 阅读器相互作用已发展成为一种有前途的癌症治疗策略。在这篇综述中，我们总结了破译 p53 的“PTM 代码”的进展，特别关注特定阅读器蛋白在功能上破译p53的这些PTM中所包含的信息的机制。我们还强调了干预 p53 PTM-reader 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“PTMomic”研究的观点。