Lysine Glutarylation Is a Protein Posttranslational Modification Regulated by SIRT5

doi:10.1016/j.cmet.2014.03.014

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	Lysine Glutarylation Is a Protein Posttranslational Modification Regulated by SIRT5
	Tan, Minjia7,8 ; Peng, Chao 9; Anderson, Kristin A.10; Chhoy, Peter 10; Xie, Zhongyu 9; Dai, Lunzhi 9; Park, Jeongsoon 11,12; Chen, Yue 9; Huang, He 9; Zhang, Yi 7,8
刊名	CELL METABOLISM
	2014-04-01
卷号	19 期号:4 页码:605-617
ISSN号	1550-4131
DOI	10.1016/j.cmet.2014.03.014
文献子类	Article
英文摘要	We report the identification and characterization of a five-carbon protein posttranslational modification (PTM) called lysine glutarylation (K-glu). This protein modification was detected by immunoblot and mass spectrometry (MS), and then comprehensively validated by chemical and biochemical methods. We demonstrated that the previously annotated deacetylase, sirtuin 5 (SIRT5), is a lysine deglutarylase. Proteome-wide analysis identified 683 Kglu sites in 191 proteins and showed that Kglu is highly enriched on metabolic enzymes and mitochondrial proteins. We validated carbamoyl phosphate synthase 1 (CPS1), the rate-limiting enzyme in urea cycle, as a glutarylated protein and demonstrated that CPS1 is targeted by SIRT5 for deglutarylation. We further showed that glutarylation suppresses CPS1 enzymatic activity in cell lines, mice, and a model of glutaric acidemia type I disease, the last of which has elevated glutaric acid and glutaryl-CoA. This study expands the landscape of lysine acyl modifications and increases our understanding of the deacylase SIRT5.
资助项目	NIH[GM105933] ; NIH[CA160036] ; NIH[RR020839] ; NIH[GM101171] ; NIH[CA177925] ; NIH[AG000114] ; Nancy and Leonard Florsheim Family Fund[00000000] ; National Science and Technology Major Project of the Ministry of Science and Technology of China[2012ZX09301001-007] ; Natural Science Foundation of China[31370814] ; Shanghai Pujiang Program[13PJ1410300] ; American Heart Association[12SDG8840004] ; American Heart Association[12IRG9010008] ; Edward Mallinckrodt Jr. Foundation[00000000] ; Ellison Medical Foundation[00000000] ; National Institutes of Health[AA022146] ; National Institutes of Health[AG045351] ; Duke O'Brien Center for Kidney Research[5P30DK096493-02] ; NCI[CA059365-19] ; Danish Independent Research Council-Technology and Production Sciences (Sapere Aude grant)[12-132328] ; Danish Independent Research Council-Natural Sciences (Steno grant)[10-080907] ; Villum Foundation[00000000] ; Carlsberg Foundation[00000000] ; German Research Foundation (Deutsche Forschungsgemeinschaft)[MU1778/3-1] ; NIH/NIGMS[5T32GM007105-40]
WOS关键词	CARBAMOYL-PHOSPHATE SYNTHETASE ; ACETYL-COENZYME-A ; HISTONE ACETYLATION ; MOUSE MODEL ; SUCCINYLATION ; ENZYME ; IDENTIFICATION ; TRANSCRIPTION ; BIOSYNTHESIS ; DEACETYLASES
WOS研究方向	Cell Biology ; Endocrinology & Metabolism
语种	英语
出版者	CELL PRESS
WOS记录号	WOS:000333751600008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277142]
专题	化学蛋白质组学研究中心中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Hirschey, Matthew D.
作者单位	1.Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA; 2.Univ Michigan, Geriatr Ctr, Ann Arbor, MI 48109 USA; 3.Tech Univ Denmark, Dept Chem, DK-2800 Lyngby, Denmark; 4.Univ Med Ctr Hamburg Eppendorf, Childrens Hosp, Dept Biochem, D-20246 Hamburg, Germany; 5.NHGRI, NIH, Bethesda, MD 20892 USA 6.Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Computat Chem & Biol Core Facil, Aurora, CO 80045 USA; 7.Chinese Acad Sci, Shanghai Inst Mat Med, Chem Prote Ctr, Shanghai 201203, Peoples R China; 8.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 9.Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA; 10.Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27704 USA;
推荐引用方式 GB/T 7714	Tan, Minjia,Peng, Chao,Anderson, Kristin A.,et al. Lysine Glutarylation Is a Protein Posttranslational Modification Regulated by SIRT5[J]. CELL METABOLISM,2014,19(4):605-617.
APA	Tan, Minjia.,Peng, Chao.,Anderson, Kristin A..,Chhoy, Peter.,Xie, Zhongyu.,...&Zhao, Yingming.(2014).Lysine Glutarylation Is a Protein Posttranslational Modification Regulated by SIRT5.CELL METABOLISM,19(4),605-617.
MLA	Tan, Minjia,et al."Lysine Glutarylation Is a Protein Posttranslational Modification Regulated by SIRT5".CELL METABOLISM 19.4(2014):605-617.