乙酰化修饰对人非组蛋白稳定性调控功能的最新进展

乙酰化修饰是一种广泛存在于生物体中的可逆性蛋白质翻译后修饰方式,主要发生于蛋白质赖氨酸残基的侧链NH2基团上,最早在组蛋白中发现。乙酰化修饰主要通过修饰组蛋白影响细胞的染色质结构以及激活细胞核内转录因子,从基因组水平来调控细胞的生命活动。随着乙酰化修饰检测技术和生物学研究的发展,发现乙酰化修饰也大量存在于非组蛋白中,并调控蛋白质的功能,进而影响多种生物学过程。其中,乙酰化修饰可以调控非组蛋白的稳定性,使其在细胞中更加稳定和持久地存在,这种调控机制在细胞的生长和分化等过程中具有重要作用,并影响多种疾病的发生发展。该文介绍了乙酰化修饰及其主要的生物学功能,系统总结了乙酰化修饰对人非组蛋白稳定性调控的机制与功能的影响,并介绍了乙酰化修饰调控蛋白质稳定性对疾病发生发展的作用,有助于解析疾病的发生机制,为疾病的治疗提供新的思路和方法。     

RPD3家族成员调控植物发育及环境应答的分子机制

赖氨酸乙酰化是翻译后修饰的主要类型之一,在调节基因表达和蛋白质功能中起关键作用。组蛋白去乙酰化酶(Histone deacetylases,HDACs)负责从组蛋白和非组蛋白的赖氨酸中去除乙酰基。RPD3家族是研究最广的HDACs,文中对拟南芥RPD3家族在多个生长发育过程中的调控机制进行了综述,为深入研究RPD3家族成员调控植物发育的机制提供参考,也为探索HDACs其他家族成员的功能提供较为清晰的研究思路。     

组蛋白乙酰基转移酶1在肝癌细胞中介导的蛋白质乙酰化修饰谱分析

赖氨酸乙酰化是重要的蛋白质翻译后修饰之一,广泛存在于细胞的生理和病理过程.组蛋白乙酰基转移酶1(HAT1)作为第一个被鉴定的蛋白ε-氨基赖氨酸乙酰基转移酶,具有介导组蛋白和非组蛋白乙酰化的作用.然而,在肝癌细胞中HAT1介导的乙酰化蛋白质及其修饰位点目前仍不清楚.本研究首先揭示了 HAT1在肝癌组织中呈高表达,并且与预...     

代谢酶乙酰化修饰对新陈代谢的调控

蛋白质的赖氨酸乙酰化修饰可以定义为在蛋白质的赖氨酸残基上添加或移除一个乙酰基团,这个过程是由乙酰化酶和脱乙酰酶调控的.真核生物细胞核内组蛋白和转录因子的可逆乙酰化修饰对基因表达调控的机制早已研究得比较清楚.1996年以来,一些独立的研究也陆续发现,参与到其他生命活动中的蛋白质存在着乙酰化修饰情况,表明乙酰化可能在生命活动中发挥着广泛的调节作用.然而直到2009年,高通量的蛋白质质谱分析技术才使得在蛋白质组水平上研究乙酰化修饰成为可能,并发现蛋白质乙酰化普遍存在.学者们发现,乙酰化修饰是一个在细胞核或细胞质的亚细胞器内广泛存在的翻译后修饰调控机制,可能参与了染色体重塑、细胞周期调控、细胞骨架的大分子运输、新陈代谢等多种生命活动.本文详细总结代谢酶的乙酰化修饰对新陈代谢调控的关键作用,并说明代谢酶的乙酰化修饰是一个从原核生物到真核生物进化上高度保守的调控机制.     

植物组蛋白去乙酰化酶的特性及功能

真核生物染色质修饰是基因表达调控中的一个重要部分,组蛋白乙酰化修饰是基因转录调控的关键机制,与基因表达的活跃与沉默密切相关。组蛋白乙酰化修饰已成为表观遗传学的重要组成部分,受到研究者的普遍重视。本文从植物组蛋白去乙酰化酶(histone deacetylase,HDACs)的分类开始,综述植物中HDACs家族成员的结构特点、组织表达的多样性与复杂性,重点阐述其对发育的调控、逆境胁迫的响应。对了解基因的调控机制,丰富表观遗传学内容,并最终应用于植物育种及农业生产具有重要意义。     

综述: 组蛋白去乙酰化酶的结构及应用

组蛋白赖氨酸乙酰化是目前研究最为广泛和深入的组蛋白翻译后修饰之一,在染色质重塑和基因表达调控等方面发挥重要作用,这种修饰在体内受到组蛋白乙酰化酶和去乙酰化酶的高度动态调控．除了以组蛋白为底物外,组蛋白去乙酰化酶还可以催化多种非组蛋白的去乙酰化,参与多种生命过程的调节．本文围绕四类人源组蛋白去乙酰化酶,综述了其分类依据、结构与功能特点、催化反应的分子机制,以及针对这些组蛋白去乙酰化酶的抑制剂和激动剂的开发和应用等方面的研究进展．     

蛋白质赖氨酸乙酰化修饰对中间代谢的调控研究

生命活动的中间代谢酶存在大量的赖氨酸乙酰化修饰作用,这些在特定位点进行的可逆的赖氨酸乙酰化修饰作用能精确地调控胞内各种代谢路径。因此,对中间代谢酶赖氨酸乙酰化的研究成为了当今热点。对中间代谢酶的乙酰化修饰的研究进展进行综述,并归纳了几种典型的中间代谢酶的可逆乙酰化作用及其乙酰化位点的分布和在中间代谢路径中重要的调控作用,以期为深入研究蛋白质乙酰化修饰提供参考。     

染色质乙酰化相关BRD蛋白家族

Bromodomain结构域首先在果蝇蛋白质Brahma中发现,折叠模式独特且高度保守,是最早也是截至目前公认唯一可与乙酰化赖氨酸结合的结构域。BRD蛋白通过结合不同的蛋白质或者定位蛋白质到细胞核发挥精细调节作用。BRD蛋白复合物常特异性识别并结合到染色质组蛋白H3/H4特定的乙酰化赖氨酸残基,从而影响靶基因的转录翻译;该蛋白复合物功能异常通常与多种疾病的发生相关联,表明对转录翻译调节有重要意义。但迄今为止,BRD蛋白复合物修饰染色质机理不明,现有研究提示BRD蛋白复合物维持染色质乙酰化状态,也可以与染色质组蛋白其它位点结合,从整体水平增强组蛋白乙酰化精度和效率。     

组蛋白乙酰化/去乙酰化与基因表达调控

组蛋白是真核生物染色质的主要成分,组蛋白修饰(如甲基化、乙酰化、磷酸化、泛素化等)在真核生物基因表达调控中发挥着重要的作用.在这些修饰中,组蛋白乙酰化/去乙酰化尤为重要.组蛋白乙酰化/去乙酰化可通过改变染色质周围电荷或参与染色质构型重建而影响基因表达;更重要的是组蛋白乙酰化/去乙酰化可形成一种特殊的“密码”,被其它蛋白质识别,影响多种蛋白质因子的活动或与其相互作用,参与到基因表达调控的整个网络中.     

蛋白质乙酰化修饰在细胞自噬中的作用进展

蛋白质翻译后修饰与细胞自噬的关系是近几年来的研究热点.自噬的发生需要多类蛋白质协同完成.在此过程中,蛋白质的乙酰化修饰对细胞自噬起着十分重要的调节作用.本文就近年来的研究从两个角度进行了总结:一方面总结了蛋白质乙酰化修饰与自噬关系的功能性研究,主要涉及组蛋白、转录因子以及与乙酰辅酶A代谢过程中相关酶的研究进展;另一方面概括了细胞自噬过程中蛋白质乙酰化修饰组学的研究进展.乙酰化酶/去乙酰化酶是蛋白质乙酰化修饰水平的主要调控者,阐明酶与底物的关系将是深入探讨乙酰化修饰与细胞自噬关系的关键所在.这些研究结果必将为揭开细胞自噬机制提供理论基础.     

Proteome-wide lysine acetylation identification in developing rice (Oryza sativa) seeds and protein co-modification by acetylation,succinylation, ubiquitination,and phosphorylation

Protein lysine acetylation is a highly conserved post-translational modification with various biological functions. However, only a limited number of acetylation sites have been reported in plants, especially in cereals, and the function of non-histone protein acetylation is still largely unknown. In this report, we identified 1003 lysine acetylation sites in 692 proteins of developing rice seeds, which greatly extended the number of known acetylated sites in plants. Seven distinguished motifs were detected flanking acetylated lysines. Functional annotation analyses indicated diverse biological processes and pathways engaged in lysine acetylation. Remarkably, we found that several key enzymes in storage starch synthesis pathway and the main storage proteins were heavily acetylated. A comprehensive comparison of the rice acetylome, succinylome, ubiquitome and phosphorylome with available published data was conducted. A large number of proteins carrying multiple kinds of modifications were identified and many of these proteins are known to be key enzymes of vital metabolic pathways. Our study provides extending knowledge of protein acetylation. It will have critical reference value for understanding the mechanisms underlying PTM mediated multiple signal integration in the regulation of metabolism and development in plants.     

Molecular characterization of propionyllysines in non-histone proteins

Lysine propionylation and butyrylation are protein modifications that were recently identified in histones. The molecular components involved in the two protein modification pathways are unknown, hindering further functional studies. Here we report identification of the first three in vivo non-histone protein substrates of lysine propionylation in eukaryotic cells: p53, p300, and CREB-binding protein. We used mass spectrometry to map lysine propionylation sites within these three proteins. We also identified the first two in vivo eukaryotic lysine propionyltransferases, p300 and CREB-binding protein, and the first eukaryotic depropionylase, Sirt1. p300 was able to perform autopropionylation on lysine residues in cells. Our results suggest that lysine propionylation, like lysine acetylation, is a dynamic and regulatory post-translational modification. Based on these observations, it appears that some enzymes are common to the lysine propionylation and lysine acetylation regulatory pathways. Our studies therefore identified first several important players in lysine propionylation pathway.     

Proteomic profiling of lysine acetylation in Pseudomonas aeruginosa reveals the diversity of acetylated proteins

Protein lysine acetylation is a reversible and highly regulated post‐translational modification with the well demonstrated physiological relevance in eukaryotes. Recently, its important role in the regulation of metabolic processes in bacteria was highlighted. Here, we reported the lysine acetylproteome of Pseudomonas aeruginosa using a proteomic approach. We identified 430 unique peptides corresponding to 320 acetylated proteins. In addition to the proteins involved in various metabolic pathways, several enzymes contributing to the lipopolysaccharides biosynthesis were characterized as acetylated. This data set illustrated the abundance and the diversity of acetylated lysine proteins in P. aeruginosa and opens opportunities to explore the role of the acetylation in the bacterial physiology.     

Quantification of Mitochondrial Acetylation Dynamics Highlights Prominent Sites of Metabolic Regulation

Lysine acetylation is rapidly becoming established as a key post-translational modification for regulating mitochondrial metabolism. Nonetheless, distinguishing regulatory sites from among the thousands identified by mass spectrometry and elucidating how these modifications alter enzyme function remain primary challenges. Here, we performed multiplexed quantitative mass spectrometry to measure changes in the mouse liver mitochondrial acetylproteome in response to acute and chronic alterations in nutritional status, and integrated these data sets with our compendium of predicted Sirt3 targets. These analyses highlight a subset of mitochondrial proteins with dynamic acetylation sites, including acetyl-CoA acetyltransferase 1 (Acat1), an enzyme central to multiple metabolic pathways. We performed in vitro biochemistry and molecular modeling to demonstrate that acetylation of Acat1 decreases its activity by disrupting the binding of coenzyme A. Collectively, our data reveal an important new target of regulatory acetylation and provide a foundation for investigating the role of select mitochondrial protein acetylation sites in mediating acute and chronic metabolic transitions.