Proteome-wide analysis of USP14 substrates revealed its role in hepatosteatosis via stabilization of FASN

doi:10.1038/s41467-018-07185-y

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	Proteome-wide analysis of USP14 substrates revealed its role in hepatosteatosis via stabilization of FASN
	Liu, Bin 6,7,8; Jiang, Shangwen 1,8; Li, Min 6; Xiong, Xuelian 6; Zhu, Mingrui 1,8; Li, Duanzhuo 7; Zhao, Lei 8; Qian, Lili 1,8; Zhai, Linhui 8; Li, Jing2
刊名	NATURE COMMUNICATIONS
	2018-11-13
卷号	9
ISSN号	2041-1723
DOI	10.1038/s41467-018-07185-y
文献子类	Article
英文摘要	Ubiquitin-specific protease 14 (USP14) is one of the major proteasome-associated deubiquitinating enzymes critical for proteome homeostasis. However, substrates of USP14 remain largely unknown, hindering the understanding of its functional roles. Here we conduct a comprehensive proteome, ubiquitinome and interactome analysis for USP14 substrate screening. Bioinformatics analysis reveals broad new potential roles of USP14, especially in lipid and carbohydrate metabolism. Among the potential substrates identified, we show that fatty acid synthase (FASN), a key enzyme involved in hepatic lipogenesis, is a bona fide substrate of USP14. USP14 directly interacts with and increases FASN stability. As a result, overexpression of USP14 promotes liver triglyceride accumulation in C57BL/6 mice, whereas genetic ablation or pharmacological inhibition of USP14 ameliorates hepatosteatosis, hyperglycemia and insulin resistance in obese mice. In conclusion, our findings reveal for the first time an indispensable role of USP14 in hepatosteatosis through FASN stabilization.
资助项目	National Key Research and Development Program of China[2016YFC1304801] ; National Basic Research Program of China (973 Program)[2014CBA02004] ; Natural Science Foundation of China[91753203] ; Natural Science Foundation of China[81773018] ; Natural Science Foundation of China[81771138] ; Special Project on Precision Medicine under the National Key RD Program[2017YFC0906600] ; Innovation Project of Instrument and Equipment Function Development of the Chinese Academy of Sciences[2060499] ; Shanghai Rising-Star Program by Science and Technology Commission of Shanghai Municipality[17QA1400800] ; K. C. Wong Education Foundation[00000000]
WOS关键词	FATTY LIVER-DISEASE ; DEUBIQUITINATING ENZYME USP14 ; UBIQUITIN-SPECIFIC PROTEASE ; DE-NOVO LIPOGENESIS ; LARGE GENE LISTS ; ACID SYNTHASE ; DIABETES-MELLITUS ; HEPATIC STEATOSIS ; PPAR-ALPHA ; CANCER
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000449926900003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279494]
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	Lu, Yan; Li, Xiaoying; Tan, Minjia
作者单位	1.Univ Chinese Acad Sci, Beijing, Peoples R China; 2.Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Dept Bioinformat & Biostat, Shanghai 200240, Peoples R China; 3.Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Anesthesiol, Shanghai 200025, Peoples R China; 4.Univ Michigan, Med Ctr, Life Sci Inst, Ann Arbor, MI 48109 USA; 5.Univ Michigan, Med Ctr, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA 6.Fudan Univ, Fudan Inst Metab Dis, Zhongshan Hosp, Dept Endocrinol & Metab,Minist Educ,Key Lab Metab, Shanghai 200032, Peoples R China; 7.Hubei Polytech Univ, Sch Med, Hubei Key Lab Kidney Dis Pathogenesis & Intervent, Huangshi 435003, Hubei, Peoples R China; 8.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Liu, Bin,Jiang, Shangwen,Li, Min,et al. Proteome-wide analysis of USP14 substrates revealed its role in hepatosteatosis via stabilization of FASN[J]. NATURE COMMUNICATIONS,2018,9.
APA	Liu, Bin.,Jiang, Shangwen.,Li, Min.,Xiong, Xuelian.,Zhu, Mingrui.,...&Tan, Minjia.(2018).Proteome-wide analysis of USP14 substrates revealed its role in hepatosteatosis via stabilization of FASN.NATURE COMMUNICATIONS,9.
MLA	Liu, Bin,et al."Proteome-wide analysis of USP14 substrates revealed its role in hepatosteatosis via stabilization of FASN".NATURE COMMUNICATIONS 9(2018).