Sirt7在病理生理活动中的作用机制  

Regulation Mechanisms of Sirt7 in Pathophysiological Activities

作　　者：鲁阳阳 李艳[1] 罗成[1] LU Yang-Yang;LI Yan;LUO Cheng(Department of Medical Biochemistry,School of Medicine,Yichun University,Yichun 336000,Jiangxi,China)

机构地区：[1]宜春学院医学院医学生化教研室,江西宜春336000

出　　处：《中国生物化学与分子生物学报》2022年第5期570-576,共7页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金项目(No.31600817);江西省大学生创新创业训练计划项目(No.S202010417035)资助。

摘　　要：沉默信息调节因子2相关酶(silent mating type information regulator 2-related enzymes,Sirtuin)是烟酰胺腺嘌呤二核苷酸(nicotinamide adenine dinucleotide,NAD+)依赖性的去乙酰化酶。Sirt7是定位于核仁的Sirtuin蛋白家族成员,除了具有去乙酰化酶活性外,还具有腺苷二磷酸(adenosine diphosphate,ADP)-核糖基转移酶、去琥珀酰化酶和去戊二酰化酶活性。Sirt7的作用底物包括组蛋白、DNA损伤修复相关因子、核仁小核糖核蛋白成分(核仁纤维蛋白、U3)、转录因子(GA结合蛋白β1(GA binding proteinβ1,GABPβ1)、叉头框蛋白O4、GATA4)、细胞周期蛋白依赖激酶9、组蛋白乙酰转移酶1、聚合酶相关因子53(polymerase associated factor 53,PAF53)、Ras相关核蛋白(Ras-related nuclear protein,Ran)、活化T细胞的核因子c1和p53等。另外,Sirt7还可以与损伤特异性DNA结合蛋白1(damage-specific DNA binding protein 1,DDB1)/cullin 4/DDB1-cullin 4相关因子1、Suv39h1/Sirt1、Myc、核呼吸因子1和Elk4等作用,进而调节其功能,但作用机制尚不清楚。Sirt7的多种活性使其在维持基因组稳定、调节RNA转录、抵御应激反应、调控代谢及炎症等病理生理活动中发挥重要作用。本文将介绍Sirt7在调节以上病理/生理活动中的作用机制,以及腺苷酸活化蛋白激酶(adenosine 5′-monophosphate activated protein kinase,AMPK)、蛋白质精氨酸甲基转移酶6、泛素特异性肽酶7等对Sirt7蛋白合成及活性的调节作用,并对目前Sirt7研究中存在的问题进行讨论。Silent mating type information regulator 2-related enzymes or sirtuin family proteins are nicotinamide adenine dinucleotide(NAD+)-dependent deacetylases.Sirt7 is a member of sirtuin family and locates in the nucleolus.In recent years,increasing studies have been conducted on Sirt7 and its functions are gradually elucidated.Besides the classic deacetylase activity,Sirt7 also possesses activities such as adenosine diphosphate(ADP)-ribosyltransferase,desuccinylase and deglutarylase.The active substrates of Sirt7 include histones,DNA damage repair related factors,small nucleolar ribonucleoprotein components(nucleolar fibrin,U3),transcription factors(GA binding proteinβ1(GABPβ1),forkhead box protein O4,GATA4),cyclin dependent kinase 9,histone acetyltransferase 1,polymerase associated factor 53(PAF53),Ras-related nuclear protein(Ran),nuclear factor of activated T cells 1,and p53,etc.Sirt7 could also regulate the functions of damage-specific DNA binding protein 1(DDB1)/cullin 4/DDB1-cullin 4 related factors 1,Suv39h1/Sirt1,Myc,nuclear respiration factor 1 and Elk4,while the mechanisms involved are still unclear.These studies imply that Sirt7 plays important roles in genome integrity,RNA transcription regulation,stress resistance,metabolic adjustment,inflammation modulation and other pathophysiological activities.This review will sort out the mechanisms of Sirt7 in regulating the activities mentioned above.The regulation of Sirt7 expression and activity by adenylate activated protein kinase(AMPK),protein arginine methyltransferase 6 and ubiquitin specific peptidase 7 are also introduced.Finally,the problems in present researchof Sirt7 are discussed.

关 键 词：去乙酰化酶 沉默信息调节因子2相关酶7 基因组稳定 RNA转录 代谢调控 

分 类 号：Q51[生物学—生物化学] Q71