| Structural highlights
3v3q is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , |
| Related: | 3v3e |
| Gene: | NR4A1, GFRP1, HMR, NAK1 (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[NR4A1_HUMAN] Orphan nuclear receptor. May act concomitantly with NURR1 in regulating the expression of delayed-early genes during liver regeneration. Binds the NGFI-B response element (NBRE) 5'-AAAAGGTCA-3' (By similarity). May inhibit NF-kappa-B transactivation of IL2.[1]
Publication Abstract from PubMed
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 AMPKalpha. 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.
The orphan nuclear receptor Nur77 regulates LKB1 localization and activates AMPK.,Zhan YY, Chen Y, Zhang Q, Zhuang JJ, Tian M, Chen HZ, Zhang LR, Zhang HK, He JP, Wang WJ, Wu R, Wang Y, Shi C, Yang K, Li AZ, Xin YZ, Li TY, Yang JY, Zheng ZH, Yu CD, Lin SC, Chang C, Huang PQ, Lin T, Wu Q Nat Chem Biol. 2012 Nov;8(11):897-904. doi: 10.1038/nchembio.1069. Epub 2012 Sep , 16. PMID:22983157[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Harant H, Lindley IJ. Negative cross-talk between the human orphan nuclear receptor Nur77/NAK-1/TR3 and nuclear factor-kappaB. Nucleic Acids Res. 2004 Oct 5;32(17):5280-90. Print 2004. PMID:15466594 doi:10.1093/nar/gkh856
- ↑ Zhan YY, Chen Y, Zhang Q, Zhuang JJ, Tian M, Chen HZ, Zhang LR, Zhang HK, He JP, Wang WJ, Wu R, Wang Y, Shi C, Yang K, Li AZ, Xin YZ, Li TY, Yang JY, Zheng ZH, Yu CD, Lin SC, Chang C, Huang PQ, Lin T, Wu Q. The orphan nuclear receptor Nur77 regulates LKB1 localization and activates AMPK. Nat Chem Biol. 2012 Nov;8(11):897-904. doi: 10.1038/nchembio.1069. Epub 2012 Sep , 16. PMID:22983157 doi:10.1038/nchembio.1069
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