ArticleProceedings of the National Academy of Sciences of the United States of America2014
Ribosomal protein-Mdm2-p53 pathway coordinates nutrient stress with lipid metabolism by regulating MCD and promoting fatty acid oxidation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 126 citations in OpenAlex.
- Dual-stress-responsive-pathways prevent HCC initiation via p53 suppression of MTHFD1L-RNA mResearch square · 2026Article
- p53: from understanding its structure to advances in therapeutic targeting.Signal transduction and targeted therapy · 2026Review
- Liver-specific delivery of MDM2 antisense oligonucleotides counteracts diet-induced metabolic-dysfunction-associated steatotic liver diseases.Molecular therapy. Nucleic acids · 2026Article
- Pathogenic Mechanisms in Cervical Cancer: Energy Metabolism, Hypoxia and Therapy.Life (Basel, Switzerland) · 2026Review
- Tackling cuproptosis: from metabolic rewiring to therapeutic exploitation in cancer.Cellular & molecular immunology · 2026Review
- [p53-SOAT1 Axis: A Novel Target for Tumor Lipid Metabolism and Therapy].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- Emerging trends in cardiovascular diseases: the impact of ferroptosis and cuproptosis on cardiomyocyte death.Molecular and cellular biochemistry · 2025Review
- Exploring the metabolic alterations in cervical cancer induced by HPV oncoproteins: From mechanisms to therapeutic targets.Biochimica et biophysica acta. Reviews on cancer · 2025Review
- Fatty acid metabolism-derived prognostic model for lung adenocarcinoma: unraveling the link to survival and immune response.Frontiers in immunology · 2025Article
- Skeletal muscle p53-depletion uncovers a mechanism of fuel usage suppression that enables efficient energy conservation.Journal of cachexia, sarcopenia and muscle · 2024Article
- High-throughput transcriptome profiling indicates ribosomal RNAs to be associated with resistance to immunotherapy in non-small cell lung cancer (NSCLC).Journal for immunotherapy of cancer · 2024Article
- HepaticiScience · 2023Article
- Low glucose metabolite 3-phosphoglycerate switches PHGDH from serine synthesis to p53 activation to control cell fate.Cell research · 2023Article
- The crisscross between p53 and metabolism in cancer.Acta biochimica et biophysica Sinica · 2023Review
- Article
- Cuproptosis: p53-regulated metabolic cell death?Cell death and differentiation · 2023Review
- Article
- Ghrelin regulating liver activity and its potential effects on liver fibrosis andFrontiers in cellular and infection microbiology · 2023Review
- The complexity of p53-mediated metabolic regulation in tumor suppression.Seminars in cancer biology · 2022Review
- Review
26 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
The tumor suppressor p53 has recently been shown to regulate energy metabolism through multiple mechanisms. However, the in vivo signaling pathways related to p53-mediated metabolic regulation remain largely uncharacterized. By using mice bearing a single amino acid substitution at cysteine residue 305 of mouse double minute 2 (Mdm2(C305F)), which renders Mdm2 deficient in binding ribosomal proteins (RPs) RPL11 and RPL5, we show that the RP-Mdm2-p53 signaling pathway is critical for sensing nutrient deprivation and maintaining liver lipid homeostasis. Although the Mdm2(C305F) mutation does not significantly affect growth and development in mice, this mutation promotes fat accumulation under normal feeding conditions and hepatosteatosis under acute fasting conditions. We show that nutrient deprivation inhibits rRNA biosynthesis, increases RP-Mdm2 interaction, and induces p53-mediated transactivation of malonyl-CoA decarboxylase (MCD), which catalyzes the degradation of malonyl-CoA to acetyl-CoA, thus modulating lipid partitioning. Fasted Mdm2(C305F) mice demonstrate attenuated MCD induction and enhanced malonyl-CoA accumulation in addition to decreased oxidative respiration and increased fatty acid accumulation in the liver. Thus, the RP-Mdm2-p53 pathway appears to function as an endogenous sensor responsible for stimulating fatty acid oxidation in response to nutrient depletion.
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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.