ArticleCell research2022
Nuclear UHRF1 is a gate-keeper of cellular AMPK activity and function.
Article in Cell research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 48 citations in OpenAlex.
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- Role of the UHRF1-KLHL6-CORO2B axis in obesity-related insulin resistance.Journal of diabetes investigation · 2026Article
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- Translational control of AMPK activity in melanoma.Cell communication and signaling : CCS · 2026Article
- UHRF1 regulates AR ubiquitination to promote the loss of AR signaling and enzalutamide resistance in progression of prostate cancer.Cell death & disease · 2026Article
- PF protects retinal pigment epithelial cells from oxidative injury by enhancing mitophagy through a CUL3-dependent AMPK/ULK1 pathway.Archives of pharmacal research · 2026Article
- AMPK at the interface of nutrient sensing, metabolic flux and energy homeostasis.Nature metabolism · 2026Review
- Role and Molecular Mechanisms of Aerobic Glycolysis in Gastrointestinal Tumors.Journal of Cancer · 2026Review
- AMPK phosphorylates WIP1 to promote DNA repair and radioresistance in cancer cells.Cell death & disease · 2025Article
- UHRF1 restricts HCoV-229E infection through epigenetic silencing of the viral receptor APN.Nature communications · 2025Article
- UHRF1-mediated HIF-1α stabilization promotes ovarian cancer through metabolic reprogramming and angiogenesis.Cell death & disease · 2025Article
- Effect and Mechanism of Qihua Tongtiao Formula (QHTTF) on Improving Glucose and Lipid Metabolism Disorders in ZDF Rats by Integrating Network Pharmacology, Metabolomics, and Biological Validation.Pharmaceuticals (Basel, Switzerland) · 2025Article
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- Multiomics reveals metformin's dual role in gut microbiome remodeling and hepatic metabolic reprogramming for MAFLD intervention.Scientific reports · 2025Article
- AMPK is necessary for Treg functional adaptation to microenvironmental stress during malignancy and viral pneumonia.The Journal of clinical investigation · 2025Article
- UHRF1-mediated epigenetic reprogramming regulates glycolysis to promote progression of B-cell acute lymphoblastic leukemia.Cell death & disease · 2025Article
- Identification of Novel Therapeutic Targets for MAFLD Based on Bioinformatics Analysis Combined with Mendelian Randomization.International journal of molecular sciences · 2025Article
- Plasma from hypertensive pregnancy patients induce endothelial dysfunction even under atheroprotective shear stress.Scientific reports · 2025Article
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20 authors at 7 institutions in 2 countries.
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Abstract
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 AMPKα1/α2, 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.
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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.