赖氨酸2-羟基异丁酰化修饰的产生、去除及功能  

The Production,Removal and Function of Lysine 2-Hydroxyisobutyrylation Modification

作　　者：冯进 张硕 万方 FENG Jin;ZHANG Shuo;WAN Fang(College of Life Sciences,Inner Mongolia Agricultural University,Hohhot 010010,China)

机构地区：[1]内蒙古农业大学,生命科学学院,呼和浩特010010

出　　处：《中国细胞生物学学报》2024年第6期1199-1210,共12页Chinese Journal of Cell Biology

基　　金：内蒙古自治区自然科学基金(批准号:2020MS08032)资助的课题。

摘　　要：赖氨酸2-羟基异丁酰化(lysine 2-hydroxyisobutyrylation,Khib)作为近年来发现的一种翻译后修饰,其结构和功能与已广泛研究的赖氨酸乙酰化有所不同。最新的质谱法鉴定和定量研究表明,组蛋白和非组蛋白均可以发生Khib,但目前尚缺少总结分析Khib的来源及功能的综述。该文总结了Khib的发现和来源,系统概述了形成和去除该修饰的酶(Writers、Erasers),以及涉及Khib的蛋白。该文介绍了组蛋白与非组蛋白上的Khib与基因转录调控,蛋白质翻译、折叠及降解,Khib蛋白参与细胞迁移和调控代谢相关酶功能等方面的相关性。此外,通过对文献报道的Khib蛋白位点进行汇总及motif分析发现了一种显著的motif特征xxKxK。对文献报道具有Khib的蛋白进行通路富集分析,富集到了蛋白质的生命周期各个环节,包括RNA模板的产生以及蛋白质的翻译、定位和降解,提示Khib可调控蛋白质命运。上述分析与总结不仅揭示了Khib的新功能,还强调了进一步深入研究Khib机制的必要性。通过探究Khib在不同生物过程中的作用机制,可以更全面地了解这种翻译后修饰对细胞功能和生物过程的调控作用,为未来开展相关疾病治疗和生物学研究提供重要的理论基础和启示。Khib(lysine 2-hydroxyisobutyrylation),discovered in recent years,is a post-translational modification with distinct structural and functional differences from the well-studied lysine acetylation.Recent mass spectrometry identification and quantification studies have shown that both histone and non-histone proteins can undergo Khib modification.However,there is currently a lack of comprehensive review summarizing the origins and functions of Khib modification.This article summarizes the discovery and sources of Khib,provides a systematic overview of the enzymes involved in the addition and removal of this modification(Writers,Erasers),and highlights proteins affected by Khib modification.The article discusses the relevance of Khib modifications on histone and non-histone proteins to aspects such as gene transcription regulation,protein translation,folding and degradation,influencing cell migration,and regulating metabolic enzyme functions.Additionally,by summarizing the Khib-modified protein sites reported in the literature and conducting motif analysis,a significant motif feature xxKxK is discovered.Pathway enrichment analysis of proteins with Khib modification reported in the literature reveals all aspects of the protein life cycle,including the production of RNA templates,and the translation,localization and degradation of proteins,suggesting that Khib can regulate protein fate.The above analysis and summary not only reveal new functions of Khib but also emphasize the necessity for further in-depth research into the mechanisms of Khib.By exploring the action mechanisms of Khib in different biological processes,a more comprehensive understanding of how this post-translational modification regulates cellular functions and biological processes can be achieved,providing important theoretical foundations and insights for future disease treatments and biological studies.

关 键 词：PTM 赖氨酸2-羟基异丁酰化 肿瘤 

分 类 号：Q75[生物学—分子生物学]