相关实验视频
Updated: Jun 23, 2025

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
Published on: March 21, 2022
CHK2-USP7轴的酸化-脱化正反循环在氧化应激下稳定了p53
Jingwei Liu1, Liangzi Cao2, Yubang Wang2
1The College of Basic Medical Science, Health Sciences Institute, China Medical University, Shenyang, Liaoning Province 110122, China; Key Laboratory of Cell Biology of the Ministry of Public Health, Key Laboratory of Medical Cell Biology of the Ministry of Education, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors of the Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging-Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, Liaoning Province 110122, China; Department of Anus and Intestine Surgery, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province 110001, China.
DNA 损伤会触发一个积极的反循环,涉及CHK2和USP7 (ubiquitin 特定蛋白酶 7). 这种机制稳定p53,对于维持细胞平衡和响应细胞应激至关重要.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- p53是细胞平衡的关键调节者,对DNA损伤和氧化应激有反应.
- USP7可使p53脱和稳定,但其精确的激活机制尚不清楚.
研究的目的:
- 阐明USP7在对DNA损伤的反应中的激活机制.
- 研究CHK2,USP7和p53信号之间的相互作用.
主要方法:
- 研究了活性氧物种 (ROS) 在DNA损伤反应中的作用.
- 用于USP7的利用化位点映射 (S168,T231) 和用于CHK2.2的二化位点映射 (K119,K131).
- 分析了甲状腺和结肠癌组织中的蛋白质水平.
主要成果:
- DNA 损伤诱导ROS,激活ATM-CHK2通路.
- CHK2可化USP7,增强其p53双化活性.
- USP7将CHK2二氧化化,使其稳定,并创建一个正反循环.
- 升高的CHK2和-USP7水平与甲状腺癌和结肠癌相关.
结论:
- 一个涉及CHK2-USP7轴的新型酸化-脱化正反循环稳定了p53.
- 这条通路对于在压力条件下维持细胞平衡至关重要.
- 异常的CHK2-USP7信号可能导致甲状腺和结肠瘤发生.
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