ArticleNature chemical biology2021
A Fbxo48 inhibitor prevents pAMPKα degradation and ameliorates insulin resistance.
Article in Nature chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
- Clinical improvement of DM1 patients reflected by reversal of disease-induced gene expression in blood.BMC medicine · 2022Trial
- MTSS1-dependent ubiquitin modifications mediated by FBXO44 remodel the actin cytoskeleton to promote gastric cancer progression.Molecular cancer · 2026Article
- AMPK at the interface of nutrient sensing, metabolic flux and energy homeostasis.Nature metabolism · 2026Review
- Endothelial KSR2 regulated by genetic variation protects against atherosclerosis through AMPKα1 stabilization.Theranostics · 2026Article
- F-box proteins in cancer: from cancer cells to the tumor microenvironment.Cell communication and signaling : CCS · 2025Review
- Hepatic glycogen directly regulates gluconeogenesis through an AMPK/CRTC2 axis in mice.The Journal of clinical investigation · 2025Article
- Serum Starvation Regulates Autophagy of Human Periodontal Ligament Cells Through Reactive Oxygen Species Mediated Adenosine Monophosphate-Activated Protein Kinase/Mechanistic Target of RAPAMYCIN Axis.International dental journal · 2025Article
- Improved Efficacy of Triple-Negative Breast Cancer Immunotherapy via Hydrogel-Based Co-Delivery of CAR-T Cells and Mitophagy Agonist.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Diagnostic Value of Serum miR-17-5p in Type 2 Diabetes Mellitus and Its Predictive Value for Chronic Complications.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Mitochondrial fission process 1 protein: a comprehensive review of its core roles in mitochondrial dynamics, disease, and therapeutic targets.Frontiers in cell and developmental biology · 2025Review
- Mangiferin alleviates diabetic pulmonary fibrosis in mice via inhibiting endothelial-mesenchymal transition through AMPK/FoxO3/SIRT3 axis.Acta pharmacologica Sinica · 2024Article
- Study on the correlation between the level of insulin resistance and changes in the degree of cerebral atherosclerosis in non-diabetic patients.Technology and health care : official journal of the European Society for Engineering and Medicine · 2024Article
- Design and Synthesis of AMPK Activators and GDF15 Inducers.Molecules (Basel, Switzerland) · 2023Article
- Review
- Translation regulation of specific mRNAs by RPS26 C-terminal RNA-binding tail integrates energy metabolism and AMPK-mTOR signaling.Nucleic acids research · 2023Article
- Mechanistic insights of soluble uric acid-induced insulin resistance: Insulin signaling and beyond.Reviews in endocrine & metabolic disorders · 2023Review
- New insights into activation and function of the AMPK.Nature reviews. Molecular cell biology · 2023Review
- The Relaxin-3 Receptor, RXFP3, Is a Modulator of Aging-Related Disease.International journal of molecular sciences · 2022Review
- Mechanisms of podocyte injury and implications for diabetic nephropathy.Clinical science (London, England : 1979) · 2022Article
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16 authors at 3 institutions in 1 country.
Funding
Abstract
The adenosine monophosphate (AMP)-activated protein kinase (Ampk) is a central regulator of metabolic pathways, and increasing Ampk activity has been considered to be an attractive therapeutic target. Here, we have identified an orphan ubiquitin E3 ligase subunit protein, Fbxo48, that targets the active, phosphorylated Ampkα (pAmpkα) for polyubiquitylation and proteasomal degradation. We have generated a novel Fbxo48 inhibitory compound, BC1618, whose potency in stimulating Ampk-dependent signaling greatly exceeds 5-aminoimidazole-4-carboxamide-1-β-ribofuranoside (AICAR) or metformin. This compound increases the biological activity of Ampk not by stimulating the activation of Ampk, but rather by preventing activated pAmpkα from Fbxo48-mediated degradation. We demonstrate that, consistent with augmenting Ampk activity, BC1618 promotes mitochondrial fission, facilitates autophagy and improves hepatic insulin sensitivity in high-fat-diet-induced obese mice. Hence, we provide a unique bioactive compound that inhibits pAmpkα disposal. Together, these results define a new pathway regulating Ampk biological activity and demonstrate the potential utility of modulating this pathway for therapeutic benefit.
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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.