【摘要】 作为最重要的抑癌因子之一，p53蛋白通过调控数百个靶基因的表达，调节细胞生理活动，维持基因组的稳定性和完整性。尽管大量研究已揭示了p53的结构特征和翻译后修饰对其功能的调控，但对于p53在激活过程中所展现出的动态行为及其精准调控靶基因表达的机制，仍缺乏系统性的理解。近年来，单细胞成像与时空组学技术的发展为解析p53的时变调控提供了全新视角。本文综述了p53调控网络的多层次结构，从分子修饰、亚细胞定位、DNA结合、染色质重塑到下游靶基因的表达动力学，系统探讨了各调控层之间的信息整合与协同作用机制。通过动态信号解码和精细调控，p53实现对细胞命运的精准调节。深入理解p53调控机制，对阐明癌症发生发展机制及开发精准干预策略具有重要意义。更多还原

【Abstract】 As one of the most important tumor suppressors,the p53 protein regulates the expression of hundreds of target genes to orchestrate diverse cellular processes and safeguard genomic stability and integrity.While extensive studies have elucidated the structural features of p53 and the role of post-translational modifications in modulating its function,a comprehensive understanding of the dynamic behavior of p53 during activation and the precise mechanisms by which it regulates target gene expression remains lacking.In recent years,advances in single-cell imaging and spatiotemporal omics have provided new insights into the time-resolved regulation of p53.This review summarizes the multilayered architecture of the p53 regulatory network,spanning molecular modifications,subcellular localization,DNA binding,chromatin remodeling,and the expression dynamics of downstream target genes.We highlight how information is integrated and coordinated across these regulatory layers.Through dynamic signal decoding and finely tuned control mechanisms,p53 achieves precise regulation of cell fate decisions.A deeper understanding of p53 regulation is critical for elucidating the mechanisms of tumorigenesis and for developing targeted therapeutic strategies.更多还原