摘要
在全球范围内,慢性肝病已成为高发生率和高死亡率的主要疾病之一。P62蛋白是一种自噬选择性底物,具有特殊结构域,目前研究较为广泛的是PB1结构域、肿瘤坏死因子受体相关因子6结合结构域和泛素结合结构域。越来越多研究表明,通过与不同信号蛋白结合,P62参与调节细胞信号转导、蛋白质更新、基因转录和表达及细胞调节因子生成等过程。本文重点围绕P62多种结构域以及P62/核转录因子红系2相关因子2,P62/NF-κB,P62/哺乳动物雷帕霉素靶蛋白和P62/环磷酸鸟苷-腺苷合成酶-干扰素基因刺激因子(cGAS-STING)轴的抗氧化应激、抗炎、蛋白质代谢调控等作用进行讨论,综述P62各结构域通过与不同功能蛋白识别和结合进而发挥调节蛋白激活与降解、能量物质代谢与生成和清除受损细胞器等功能,以及P62多种结构域翻译后修饰在不同途径下对慢性肝病发展调节的可能作用机制,为肝纤维化、酒精性脂肪肝、非酒精性脂肪肝和肝癌等慢性肝病治疗提供研究方向和新选择。
Globally,the chronic liver disease has become one of the major diseases with high inci⁃dence and mortality.P62 protein is an autophagy-selective substrate with a specific structural domain.PB1 domain,tumor necrosis factor receptor associated factor 6 binding domain and ubiquitin-associated domain are widely studied.Increasing studies have shown that by binding to different signaling proteins,P62 is able to participate in regulating cell signaling,protein renewal,gene transcriptional expression,cellular regulatory factor production and other processes.This paper focuses on the multiple structural domains of P62 and the roles of P62/nuclear factor erythroid 2-related factor 2,P62/NF-κB,P62/mammalian target of rapamycin axis and P62/cyclic GMP-AMP synthase-stimulator of interferon genes(cGAS-STING)axises in anti-oxidative stress,anti-inflammation,and regulation of protein metabolism.This paper reviews the functions of P62 structural domains in regulating the activation and degradation of various proteins,the metabolism and production of energetic substances and the clearance of damaged organelles through recognition and binding to different functional proteins.The possible mechanisms for posttranslational modifications of the P62 structural domains that regulate the development of chronic liver disease in different ways are also presented,which is expected to provide new options for therapeutic research on chronic liver diseases such as liver fibrosis,alcoholic fatty liver,non-alcoholic fatty liver and liver cancer.
作者
孙盈
赵丹雳
张昱欣
高媛媛
王君睿
邵江娟
郑仕中
SUN Ying;ZHAO Dan-li;ZHANG Yu-xin;GAO Yuan-yuan;WANG Jun-rui;SHAO Jiang-juan;ZHENG Shi-zhong(Jiangsu Key Laboratory of Pharmacology and Safety Evaluation of Chinese Materia Medica,Nanjing University of Chinese Medicine,Nanjing 210023,China;Jiangsu Key Laboratory of Substances of Chinese Medicine,Nanjing University of Chinese Medicine,Nanjing 210023,China)
出处
《中国药理学与毒理学杂志》
CAS
北大核心
2023年第2期142-149,共8页
Chinese Journal of Pharmacology and Toxicology
基金
国家自然科学基金(82274185)
国家自然科学基金(82073914)
江苏省高等学校自然科学研究重大项目(19KJA310005)
大学生创新创业训练计划项目(202210315143Z)。
关键词
P62
慢性肝病
氧化应激
炎症
能量代谢
p62
chronic liver disease
oxidative stress
inflammation
energy metabolism
