ArticleCell metabolism2023
Neddylation of phosphoenolpyruvate carboxykinase 1 controls glucose metabolism.
Article in Cell metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- PSMA6 drives non-small cell lung cancer progression by stabilizing NEDD8 and activating NF-κB signaling.Translational lung cancer research · 2026Article
- Neddylation as a molecular integrator of metabolic dysfunction and endothelial dysfunction in type 2 diabetes.Acta pharmacologica Sinica · 2026Review
- Protein neddylation as a therapeutic target: challenges and opportunities.The Journal of clinical investigation · 2026Review
- Neddylation: from regulatory mechanisms to clinical implications in cancer.Journal of advanced research · 2026Review
- Role of neddylation in diabetes metabolism: potential therapeutic target.Journal of diabetes and metabolic disorders · 2026Review
- Hepatic HuR modulates glucose metabolism through the C/EBPβ/PCK1 pathway.Molecular metabolism · 2026Article
- Revitalizing p-GSK-3β via cysteine sulfenylation promotes hepatic insulin resistance by differentially regulating glycogenesis and gluconeogenesis.Nature metabolism · 2026Article
- [Endogenous neddylation in B cells regulates immune responses in mice].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Article
- RNF187 neddylation in pancreatic cancer activates malignancy via IQGAP1-dependent actin cytoskeleton rearrangement.Oncogene · 2026Article
- Naringin Mitigates PEDV-Induced Intestinal Damage in Suckling Piglets by Modulating Inflammatory, Antiviral, and Metabolic and Transport Pathways.Biomolecules · 2025Article
- Emerging Roles of Post-Translational Modifications in Metabolic Homeostasis and Type 2 Diabetes.International journal of molecular sciences · 2025Review
- A comparative proteomic, transcriptomic and glycomic analysis of extracellular vesicle isolation techniques highlights ExoGAG efficiency for a more complete identification of breast milk molecular signaling pathways.Cell communication and signaling : CCS · 2025Article
- Ubiquitination and ubiquitin-like modifications in metabolic dysfunction-associated steatotic liver disease: mechanisms and implications.BMB reports · 2025Review
- NEDDylation Regulates CD8+ T-cell Metabolism and Antitumor Immunity.Cancer immunology research · 2025Article
- Deciphering the roles of neddylation modification in hepatocellular carcinoma: Molecular mechanisms and targeted therapeutics.Genes & diseases · 2025Review
- The neglected PCK1/glucagon (inter)action in nutrient homeostasis beyond gluconeogenesis: Disease pathogenesis and treatment.Molecular metabolism · 2025Review
- SF1-specific deletion of the energy sensor AMPKγ2 induces obesity.Molecular metabolism · 2025Article
- Screening and regulatory mechanisms of biomarkers related to neddylation in laryngeal squamous cell carcinoma.Frontiers in molecular biosciences · 2025Article
- Steering toward new horizons: a vision for the future of theAmerican journal of physiology. Regulatory, integrative and comparative physiology · 2024Article
- PCK1 as a target for cancer therapy: from metabolic reprogramming to immune microenvironment remodeling.Cell death discovery · 2024Review
Corrections and comments
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Authors and funding
28 authors at 9 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neddylation is a post-translational mechanism that adds a ubiquitin-like protein, namely neural precursor cell expressed developmentally downregulated protein 8 (NEDD8). Here, we show that neddylation in mouse liver is modulated by nutrient availability. Inhibition of neddylation in mouse liver reduces gluconeogenic capacity and the hyperglycemic actions of counter-regulatory hormones. Furthermore, people with type 2 diabetes display elevated hepatic neddylation levels. Mechanistically, fasting or caloric restriction of mice leads to neddylation of phosphoenolpyruvate carboxykinase 1 (PCK1) at three lysine residues-K278, K342, and K387. We find that mutating the three PCK1 lysines that are neddylated reduces their gluconeogenic activity rate. Molecular dynamics simulations show that neddylation of PCK1 could re-position two loops surrounding the catalytic center into an open configuration, rendering the catalytic center more accessible. Our study reveals that neddylation of PCK1 provides a finely tuned mechanism of controlling glucose metabolism by linking whole nutrient availability to metabolic homeostasis.
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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 Socratic graph.