Nuclear UHRF1 is a gate-keeper of cellular AMPK activity and function

doi:10.1038/s41422-021-00565-y

	Nuclear UHRF1 is a gate-keeper of cellular AMPK activity and function
	Xu, Xiang 1,2,3,4; Ding, Guangjin 2,3; Liu, Caizhi 2,3; Ding, Yuhan 2,3; Chen, Xiaoxin 2,3; Huang, Xiaoli 5,6; Zhang, Chen-Song 7; Lu, Shanxin 7; Zhang, Yunpeng 2,3; Huang, Yuanyong 2,3
刊名	CELL RESEARCH
	2021-09-24
页码	18
ISSN号	1001-0602
DOI	10.1038/s41422-021-00565-y
通讯作者	Ma, Xinran(xrma@bio.ecnu.edu.cn) ; Wong, Jiemin(jmweng@bio.ecnu.edu.cn)
英文摘要	The AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis. Although much has been learned on how low energy status and glucose starvation activate AMPK, how AMPK activity is properly controlled in vivo is still poorly understood. Here we report that UHRF1, an epigenetic regulator highly expressed in proliferating and cancer cells, interacts with AMPK and serves to suppress AMPK activity under both basal and stressed conditions. As a nuclear protein, UHRF1 promotes AMPK nuclear retention and strongly suppresses nuclear AMPK activity toward substrates H2B and EZH2. Importantly, we demonstrate that UHRF1 also robustly inhibits AMPK activity in the cytoplasm compartment, most likely as a consequence of AMPK nucleocytoplasmic shuttling. Mechanistically, we found that UHRF1 has no obvious effect on AMPK activation by upstream kinases LKB1 and CAMKK2 but inhibits AMPK activity by acting as a bridging factor targeting phosphatase PP2A to dephosphorylate AMPK. Hepatic overexpression of UHRF1 showed profound effects on glucose and lipid metabolism in wild-type mice but not in those with the liver-specific knockout of AMPK alpha 1/alpha 2, whereas knockdown of UHRF1 in adipose tissue led to AMPK activation and reduced sizes of adipocytes and lipogenic activity, highlighting the physiological significance of this regulation in glucose and lipid metabolism. Thus, our study identifies UHRF1 as a novel AMPK gate-keeper with critical roles in cellular metabolism.
资助项目	Ministry of Science and Technology of China[2017YFA054201] ; National Natural Science Foundation of China[91957120] ; National Natural Science Foundation of China[31730048] ; National Natural Science Foundation of China[31961133009] ; Shanghai Science and Technology Committee[20JC1411500]
WOS关键词	ACTIVATED PROTEIN-KINASE ; EPIGENETIC INHERITANCE ; UPSTREAM KINASE ; ENERGY SENSOR ; PHOSPHORYLATION ; METABOLISM ; GLUCOSE ; LKB1 ; INACTIVATION ; INHIBITOR
WOS研究方向	Cell Biology
语种	英语
出版者	SPRINGERNATURE
WOS记录号	WOS:000698898000004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/297536]
专题	中国科学院上海药物研究所
通讯作者	Ma, Xinran; Wong, Jiemin
作者单位	1.Fudan Univ, Zhongshan Xuhui Hosp, Shanghai, Peoples R China 2.East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Shanghai, Peoples R China 3.East China Normal Univ, Sch Life Sci, Shanghai, Peoples R China 4.Fudan Univ, Shanghai Key Lab Med Epigenet, Int Colab Med Epigenet & Metab, Minist Sci & Technol,Inst Biomed Sci, Shanghai, Peoples R China 5.Zhejiang Univ, Dept Biochem, Sch Med, Affiliated Hosp 2, Hangzhou, Zhejiang, Peoples R China 6.Zhejiang Univ, Dept Cardiol, Sch Med, Affiliated Hosp 2, Hangzhou, Zhejiang, Peoples R China 7.Xiamen Univ, Innovat Ctr Cell Signaling Network, Sch Life Sci, State Key Lab Cellular Stress Biol, 4221 South Xiangan Rd, Xiamen, Fujian, Peoples R China 8.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China 9.Zhejiang Univ, Dept Biochem & Mol Biol, Program Mol & Cell Biol, Sch Med, Hangzhou, Zhejiang, Peoples R China 10.Fengxian Dist Cent Hosp, Joint Ctr Translat Med, 6600 Nanfeng Rd, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Xu, Xiang,Ding, Guangjin,Liu, Caizhi,et al. Nuclear UHRF1 is a gate-keeper of cellular AMPK activity and function[J]. CELL RESEARCH,2021:18.
APA	Xu, Xiang.,Ding, Guangjin.,Liu, Caizhi.,Ding, Yuhan.,Chen, Xiaoxin.,...&Wong, Jiemin.(2021).Nuclear UHRF1 is a gate-keeper of cellular AMPK activity and function.CELL RESEARCH,18.
MLA	Xu, Xiang,et al."Nuclear UHRF1 is a gate-keeper of cellular AMPK activity and function".CELL RESEARCH (2021):18.