摘要
p53是细胞内最重要的抑癌蛋白质之一;细胞对p53分子功能的调控主要通过一系列翻译后修饰(PTMs)完成。其中,乙酰化修饰既可在总体水平调控p53的转录活性,又可位点特异性地调控p53依赖的转录选择性,进而精确控制p53在细胞周期阻滞、凋亡、衰老、自噬和代谢等关键生物学过程中的作用。本综述以p53乙酰化修饰研究的时间脉络为轴,首先总结了发生在p53各结构域内乙酰化修饰的建立机制,包括催化p53位点特异性乙酰化发生的乙酰基转移酶,以及各位点乙酰化修饰对p53分子功能调节的机制。其次,本综述总结了参与去除p53乙酰化修饰的关键去乙酰基酶家族,以及这些因子参与调控p53分子功能的生物学意义。同时,本文综述了能够特异性读取p53乙酰化修饰状态的识别蛋白质,以及这些识别蛋白质与p53互作,进而协同调控下游靶基因转录的分子调控网络。此外,本文概述了p53乙酰化修饰与其它类型翻译后修饰之间的“交谈”,以及这些修饰之间通过时空特异互作方式影响p53功能的分子机制。最后,本文基于p53乙酰化修饰,对肿瘤分子医学的研究前景进行讨论与展望。
p53 represents one of the most important tumor suppressors in mammalian cells,and the posttranslational modifications(PTMs)serve as a major strategy for fine-tuning of the functions of p53 in cells.Particularly,the acetylation regulates either the overall transactivity of p53 or the p53-dependent transcriptional selectivity,which plays key roles in modulating a variety of biological processes including cell cycle arrest,apoptosis,senescence,autophagy,and metabolism.This review,starting with the timeline of the researches on p53 acetylation,firstly summarizes how the site-specific acetylation of p53 is built up,including the acetyltransferases that catalyze p53 acetylation and their regulatory mechanism that influencing p53 functions.Secondly,this review summarizes pivotal deacetylases that erase p53 acetylation,and their contributions in modulating p53 cellular activities.Additionally,this review summarizes the reader proteins that specifically recognize and bind to acetylated/unacetylated residues of p53,and their intimate interactions with p53 in manipulating downstream targets transcriptions.Meanwhile,this review sums up the crosstalk mechanisms between the acetylation and other PTMs in regulating p53 biological functions.Lastly,this review proposes a perspective on the studies of p53 acetylation in the field of molecular biomedicine in future.
作者
闫晓俊
文佳
王冬来
YAN Xiao-Jun;WEN Jia;WANG Dong-Lai(Department of Medical Genetics,Institute of Basic Medical Sciences Chinese Academy of Medical Sciences and School of Basic Medicine Peking Union Medical College,Beijing 100005,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2022年第8期971-980,共10页
Chinese Journal of Biochemistry and Molecular Biology
基金
国家自然科学基金(No.81872311,82073132,82122054)
北京市自然科学基金(No.7192126)资助。
关键词
抑癌蛋白p53
乙酰化
翻译后修饰
交谈
肿瘤
tumor suppressor p53
acetylation
posttranslational modification
crosstalk
tumor
