ArticleNature chemical biology2012
The orphan nuclear receptor Nur77 regulates LKB1 localization and activates AMPK.
Article in Nature chemical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
108 citing papers in PubMed, 1 synthesis or guideline pooled it, 181 citations in OpenAlex.
- Pooled it
- Article
- A Commentary on Dual Orphan Nuclear Receptor 4A1 (NR4A1) and NR4A2 Ligands.Journal of cellular immunology · 2026Article
- Disruption of heme homeostasis by nuclear receptor Nur77 induces pyroptosis through granzyme B-dependent GSDMC cleavage.Signal transduction and targeted therapy · 2025Article
- Energy stress-induced PKCζ S-glutathionylation is essential for LKB1 cytoplasmic translocation and AMPK activation.Life metabolism · 2025Article
- Comparative Profiling and Chemogenomics Application of Chemical Tools for NR4A Nuclear Receptors.Journal of medicinal chemistry · 2025Article
- The GRK2/AP-1 Signaling Axis Mediates Vascular Endothelial Dysfunction and Atherosclerosis Induced by Oscillatory Low Shear Stress.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- From Nuclear Receptor Regulation to Spleen Activating and Accumulation Resolving Therapy: A Review of Traditional Chinese Medicine Against Diabetes and Inflammation.International journal of molecular sciences · 2025Review
- Structural and mechanistic profiling of Nurr1 modulation by vidofludimus enables structure-guided ligand design.Communications chemistry · 2025Article
- Bile acids target an exposed cavity in the glucocorticoid receptor modulating receptor self-assembly, chromatin binding and transcriptional activity.bioRxiv : the preprint server for biology · 2025Article
- Perfluorooctane Sulfonate (PFOS) and Related Compounds Induce Nuclear Receptor 4A1 (NR4A1)-Dependent Carcinogenesis.Chemical research in toxicology · 2025Article
- Controversy and multiple roles of the solitary nucleus receptor Nur77 in disease and physiology.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- NR4A1 deficiency promotes carotid plaque vulnerability by activating integrated stress response via targeting Bcat1.Cellular and molecular life sciences : CMLS · 2025Article
- The orphan nuclear receptor Nr4a1 contributes to interstitial cardiac fibrosis via modulation of cardiac fibroblast and macrophage phenotype.Cellular and molecular life sciences : CMLS · 2024Article
- Discovery of a novel exceptionally potent and orally active Nur77 ligand NB1 with a distinct binding mode for cancer therapy.Acta pharmaceutica Sinica. B · 2024Article
- Review
- LKB1 biology: assessing the therapeutic relevancy of LKB1 inhibitors.Cell communication and signaling : CCS · 2024Review
- Semaglutide ameliorates cardiac remodeling in male mice by optimizing energy substrate utilization through the Creb5/NR4a1 axis.Nature communications · 2024Article
- Natural products and synthetic analogs as selective orphan nuclear receptor 4A (NR4A) modulators.Histology and histopathology · 2024Review
48 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
25 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 AMPKα. 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.