The orphan nuclear receptor Nur77 regulates LKB1 localization and activates AMPK

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	The orphan nuclear receptor Nur77 regulates LKB1 localization and activates AMPK
	Zhan, Yan-yan ; Chen, Yan ; Zhang, Qian ; Zhuang, Jia-jia ; Tian, Min ; Chen, Hang-zi ; Zhang, Lian-ru ; Zhang, Hong-kui ; He, Jian-ping ; Wang, Wei-jia ; Wu, Rong ; Wang, Yuan ; Shi, Chunfang ; Yang, Kai ; Li, An-
刊名	http://dx.doi.org/10.1038/NCHEMBIO.1069
	2012-11
关键词	ACETYL-COA CARBOXYLASE LIGAND-BINDING DOMAIN FATTY-ACID OXIDATION PROTEIN-KINASE AMPK GLUCOSE-METABOLISM TUMOR-SUPPRESSOR SKELETAL-MUSCLE RETINOIC ACID PHOSPHORYLATION LIVER
英文摘要	Ministry of Science and Technology [2011CB910802]; National Natural Science Fund of China [30810103905, 30630070, 30921005, 30870479]; Program of Introducing Talents of Discipline to Universities [B12001, B06016]; Open Research Fund of State Key Laboratory of Cellular Stress Biology, Xiamen University [SKLCSB2012KF002]; Liver kinase B1 (LKB1) has important roles in governing energy homeostasis by regulating the activity of the energy sensor kinase AMP-activated protein kinase (AMPK). The regulation of LKB1 function, however, is still poorly understood. Here we demonstrate that the orphan nuclear receptor Nur77 binds and sequesters LKB1 in the nucleus, thereby attenuating AMPK activation. This Nur77 function is antagonized by the chemical compound ethyl 2-[2,3,4-trimethoxy-6-(1-octanoyl)phenyl]acetate (TMPA), which interacts with Nur77 with high affinity and at specific sites. TMPA binding of Nur77 results in the release and shuttling of LKB1 to the cytoplasm to phosphorylate AMPK alpha. Moreover, TMPA effectively reduces blood glucose and alleviates insulin resistance in type II db/db and high-fat diet-and streptozotocin-induced diabetic mice but not in diabetic littermates with the Nur77 gene knocked out. This study attains a mechanistic understanding of the regulation of LKB1-AMPK axis and implicates Nur77 as a new and amenable target for the design and development of therapeutics to treat metabolic diseases.
语种	英语
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/64999]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Zhan, Yan-yan,Chen, Yan,Zhang, Qian,et al. The orphan nuclear receptor Nur77 regulates LKB1 localization and activates AMPK[J]. http://dx.doi.org/10.1038/NCHEMBIO.1069,2012.
APA	Zhan, Yan-yan.,Chen, Yan.,Zhang, Qian.,Zhuang, Jia-jia.,Tian, Min.,...&Li, An-.(2012).The orphan nuclear receptor Nur77 regulates LKB1 localization and activates AMPK.http://dx.doi.org/10.1038/NCHEMBIO.1069.
MLA	Zhan, Yan-yan,et al."The orphan nuclear receptor Nur77 regulates LKB1 localization and activates AMPK".http://dx.doi.org/10.1038/NCHEMBIO.1069 (2012).