Ribosomal protein–Mdm2–p53 pathway coordinates nutrient stress with lipid metabolism by regulating MCD and promoting fatty acid oxidation
Copyright policy )Ribosomal protein–Mdm2–p53 pathway coordinates nutrient stress with lipid metabolism by regulating MCD and promoting fatty acid oxidation
SignificanceAlthough progress has been made in the characterization of p53 in regulating metabolism, very little is known about the signaling pathways involved in this regulation in response to stress in vivo. Here we show thatp53controls hepatic fatty acid oxidation in mice in response to fasting. Disruption of ribosome protein (RP)-mouse double minute (Mdm)2 binding inMdm2C305Fmice results in fasting-induced hepatosteatosis. A full-dosage ofp53and an intact RP-Mdm2-p53 pathway are required for the induction of malonyl coA decarboxylase (MCD), a critical regulator of fatty acid oxidation. Thus, the RP-Mdm2-p53 pathway functions as a key regulator of hepatic lipid homeostasis in response to nutrient deprivation stress, a function that has implications in organismal survival and tumor suppression.
- Wake Forest University United States
- Xuzhou Medical College China (People's Republic of)
- University of North Carolina at Chapel Hill United States
- UNC Lineberger Comprehensive Cancer Center United States
Mice, Knockout, Ribosomal Proteins, Carboxy-Lyases, Reverse Transcriptase Polymerase Chain Reaction, Fatty Acids, Immunoblotting, Proto-Oncogene Proteins c-mdm2, Fasting, Fibroblasts, Embryo, Mammalian, Lipid Metabolism, Fatty Liver, Mice, Stress, Physiological, Animals, Animal Nutritional Physiological Phenomena, Oxidation-Reduction, Cells, Cultured, Oligonucleotide Array Sequence Analysis, Protein Binding
Mice, Knockout, Ribosomal Proteins, Carboxy-Lyases, Reverse Transcriptase Polymerase Chain Reaction, Fatty Acids, Immunoblotting, Proto-Oncogene Proteins c-mdm2, Fasting, Fibroblasts, Embryo, Mammalian, Lipid Metabolism, Fatty Liver, Mice, Stress, Physiological, Animals, Animal Nutritional Physiological Phenomena, Oxidation-Reduction, Cells, Cultured, Oligonucleotide Array Sequence Analysis, Protein Binding
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