物理学进展 ›› 2025, Vol. 45 ›› Issue (6): 281-292.doi: 10.13725/j.cnki.pip.2025.06.002

• • 上一篇    

p53 介导的基因表达调控及其机制解

陈云翔,周邦彦,赵沛燚,吴人杰 ,刘 锋   

  1. 南京大学物理学院,南京 210093
  • 出版日期:2025-12-20 发布日期:2026-01-05

Mechanistic insights into p53-mediated gene expression regulation

CHEN Yunxiang, ZHOU Bangyan, ZHAO Peiyi, WU Renjie , LIU Feng   

  1. School of Physics, Nanjing University, Nanjing 210093, China
  • Online:2025-12-20 Published:2026-01-05
  • Supported by:
    到国家自然科学基金委面上项目 (No. 11874209)

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。

关键词: 转录调控, DNA 结合, 应激响应, 动力学特性, 相分离, 单细胞成像, 靶基因选择性

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. 

Key words: transcriptional regulation, DNA binding, stress response, dynamical properties, phase separation, single-cell imaging, target gene selctivity

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