ArticleHepatology (Baltimore, Md.)2015
Phosphorylation of the nuclear receptor corepressor 1 by protein kinase B switches its corepressor targets in the liver in mice.
Article in Hepatology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 57 citations in OpenAlex.
- Polystyrene nanoplastics induce hepatic steatosis by disrupting autophagic degradation of NCoR1 and suppressing PPARα-mediated fatty acid oxidation.Journal of nanobiotechnology · 2026Article
- Nuclear receptor coregulator interactions: beyond the switch.Genes & development · 2026Review
- Downregulation of the NF-κB protein p65 is a shared phenotype among most anti-aging interventions.GeroScience · 2025Article
- Cell-intrinsic insulin signaling defects in human iPS cell-derived hepatocytes in type 2 diabetes.The Journal of clinical investigation · 2025Article
- Liver gene expression and its rewiring in hepatic steatosis are controlled by PI3Kα-dependent hepatocyte signaling.PLoS biology · 2025Article
- Nuclear receptor corepressors non-canonically drive glucocorticoid receptor-dependent activation of hepatic gluconeogenesis.Nature metabolism · 2024Article
- p21-activated kinase 4 suppresses fatty acid β-oxidation and ketogenesis by phosphorylating NCoR1.Nature communications · 2023Article
- Genetic deletion of hepatic NCOR1 protects from atherosclerosis by promoting alternative bile acid-metabolism and sterol excretion.Cardiovascular diabetology · 2023Article
- Insights into the function of HDAC3 and NCoR1/NCoR2 co-repressor complex in metabolic diseases.Frontiers in molecular biosciences · 2023Review
- Pharmacological inhibition of Lin28 promotes ketogenesis and restores lipid homeostasis in models of non-alcoholic fatty liver disease.Nature communications · 2022Article
- Transcriptional control of energy metabolism by nuclear receptors.Nature reviews. Molecular cell biology · 2022Review
- Macrophage Nuclear Receptor Corepressor 1 Deficiency Protects Against Ischemic Stroke in Mice.Journal of cardiovascular translational research · 2022Article
- Regulation of Intestinal UDP-Glucuronosyltransferase 1A1 by the Farnesoid X Receptor Agonist Obeticholic Acid Is Controlled by Constitutive Androstane Receptor through Intestinal Maturation.Drug metabolism and disposition: the biological fate of chemicals · 2021Article
- Review
- Gene-Specific Actions of Transcriptional Coregulators Facilitate Physiological Plasticity: Evidence for a Physiological Coregulator Code.Trends in biochemical sciences · 2020Review
- Intramuscular accumulation of pentadecanoic acid activates AKT1 to phosphorylate NCOR1 and triggers FOXM1-mediated apoptosis in the pathogenesis of sarcopenia.American journal of translational research · 2020Article
- Role of the Nuclear Receptor Corepressor 1 (NCOR1) in Atherosclerosis and Associated Immunometabolic Diseases.Frontiers in immunology · 2020Review
- Hepatocyte-specific loss of GPS2 in mice reduces non-alcoholic steatohepatitis via activation of PPARα.Nature communications · 2019Article
- Autophagy regulates lipid metabolism through selective turnover of NCoR1.Nature communications · 2019Article
- The class 3 PI3K coordinates autophagy and mitochondrial lipid catabolism by controlling nuclear receptor PPARα.Nature communications · 2019Article
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Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
Abstract
unlabelledNuclear receptor corepressor 1 (NCoR1) is a transcriptional coregulator that has wide-ranging effects on gene expression patterns. In the liver, NCoR1 represses lipid synthesis in the fasting state, whereas it inhibits activation of peroxisome proliferator-activated receptor alpha (PPARα) upon feeding, thereby blunting ketogenesis. Here, we show that insulin by activation of protein kinase B induces phosphorylation of NCoR1 on serine 1460, which selectively favors its interaction with PPARα and estrogen-related receptor alpha (ERRα) over liver X receptor alpha (LXRα). Phosphorylation of NCoR1 on S1460 selectively derepresses LXRα target genes, resulting in increased lipogenesis, whereas, at the same time, it inhibits PPARα and ERRα targets, thereby attenuating oxidative metabolism in the liver. Phosphorylation-gated differential recruitment of NCoR1 to different nuclear receptors explains the apparent paradox that liver-specific deletion of NCoR1 concurrently induces both lipogenesis and oxidative metabolism owing to a global derepression of LXRα, PPARα, and ERRα activity.
conclusionPhosphorylation-mediated recruitment switch of NCoR1 between nuclear receptor subsets provides a mechanism by which corepressors can selectively modulate liver energy metabolism during the fasting-feeding transition.
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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.