Tat翻译后修饰调控HIV-1的转录  

The regulation of HIV-1 transcription by post-translational modifications of Tat

作　　者：徐骞 吴雪华[2] 钱峰[2] 刘锦[2] XU Qian;WU Xuehua;QIAN Feng;LIU Jin(Suzhou Medical College of Soochow University,Suzhou 215131,China;The Affiliated Infectious Diseases Hospital of Soochow University,Suzhou 215131,China)

机构地区：[1]苏州大学苏州医学院,苏州215131 [2]苏州大学附属传染病医院,苏州215131

出　　处：《生命的化学》2023年第11期1727-1736,共10页Chemistry of Life

基　　金：国家自然科学基金青年项目(82002194);江苏省“双创博士”-世界名校类;江苏省青年人才托举工程;苏州市民生科技项目(SYS2020189);苏州市科教兴卫项目(KJXW2019046);苏州市姑苏卫生人才计划(GSWS2021050)。

摘　　要：HIV-1病毒感染机体靶细胞后,可通过一系列调控蛋白和辅助蛋白来改变宿主环境,以逃避免疫反应和促进病毒复制。调控蛋白Tat在病毒初始转录阶段与多种转录辅助因子相互作用,控制HIV-1基因组转录和潜伏期病毒的激活等,被称为HIV-1的反式转录激活因子。翻译后修饰是一种可逆过程,在Tat与不同转录辅助蛋白之间扮演了至关重要的角色。磷酸化可以促进Tat与TAR RNA结合,乙酰化能够巩固Tat/P-TEFb/TAR RNA复合体的形成,或增加染色质修饰和重塑,增强HIV-1基因组转录起始。Tat发生泛素化修饰可导致其表达下降并阻断转录,也可表现为其水平的稳定。Tat甲基化后对转录的影响不同,甚至完全相反。因此,这可能成为逆转录病毒复制和传播的潜在靶点。本文就Tat在HIV-1基因组转录和复制中涉及蛋白质磷酸化、乙酰化、泛素化和甲基化修饰方面的研究进展进行总结,以促进人们对Tat翻译后修饰与HIV-1转录机制的理解,并为抗HIV转录的新型药物发掘奠定理论基础。The HIV-1 virus possesses the ability to modify the host environment through the utilization of regulatory and co-proteins subsequent to its entry into target cells.This mechanism serves to augment viral replication and facilitate evasion of the immune response.Among these regulatory proteins,Tat is recognized for its interaction with diverse transcriptional cofactors during the initial transcriptional phase of the virus,thereby functioning as a trans-transcriptional activator of HIV-1.Tat exerts control over the transcription of the HIV-1 genome and the activation of latent virus.Post-translational modification,a reversible process,assumes a significant role in the interactions between Tat and various transcriptional accessory proteins.Phosphorylation has the potential to facilitate the interaction between Tat and TAR RNA.Acetylation,on the other hand,has the ability to augment the formation of the Tat/P-TEFb/TARRNA complex or modify and restructure chromatin.Additionally,acetylation can promote the initiation of transcription for the HIV-1 genome.The ubiquitin modification of Tat not only reduces its expression and hinders transcription,but also confers stability at its level.The effects of Tat methylation on transcription are variable and can even be contradictory.Consequently,Tat methylation could serve as a promising target for retroviral replication and transmission.This paper provides a comprehensive overview of Tat's research advancements pertaining to protein phosphorylation,acetylation,ubiquitin,and methylation modifications in the transcription and replication of the HIV-1 genome.The primary objective is to augment comprehension of the post-translational modification mechanism of Tat and its impact on HIV-1 transcription.Ultimately,this endeavor aims to establish a theoretical framework for the identification and development of novel anti-HIV transcription drugs.

关 键 词：人类免疫缺陷病毒1型 反式转录激活因子 翻译后修饰 转录 

分 类 号：R512.91[医药卫生—内科学]