title: p73 regulates basal and starvation-induced liver metabolism in vivo.
abstract: As a member of the p53 gene family, p73 regulates cell cycle arrest, apoptosis, neurogenesis, immunity and inflammation. Recently, p73 has been shown to transcriptionally regulate selective metabolic enzymes, such as cytochrome c oxidase subunit IV isoform 1, glucose 6-phosphate dehydrogenase and glutaminase-2, resulting in significant effects on metabolism, including hepatocellular lipid metabolism, glutathione homeostasis and the pentose phosphate pathway. In order to further investigate the metabolic effect of p73, here, we compared the global metabolic profile of livers from p73 knockout and wild-type mice under both control and starvation conditions. Our results show that the depletion of all p73 isoforms cause altered lysine metabolism and glycolysis, distinct patterns for glutathione synthesis and Krebs cycle, as well as an elevated pentose phosphate pathway and abnormal lipid accumulation. These results indicate that p73 regulates basal and starvation-induced fuel metabolism in the liver, a finding that is likely to be highly relevant for metabolism-associated disorders, such as diabetes and cancer.
authors.affiliation: Institute of Pharmacology, University of Bern, Bern, Switzerland.
authors.forename: Zhaoyue
authors.initials: Z
authors.lastname: He
authors.affiliation: Medical Research Council, Toxicology Unit, Leicester, United Kingdom.|Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Agostini
authors.affiliation: Institute of Pharmacology, University of Bern, Bern, Switzerland.
authors.forename: He
authors.initials: H
authors.lastname: Liu
authors.affiliation: Medical Research Council, Toxicology Unit, Leicester, United Kingdom.|Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Gerry
authors.initials: G
authors.lastname: Melino
authors.affiliation: Institute of Pharmacology, University of Bern, Bern, Switzerland.
authors.forename: Hans-Uwe
authors.initials: HU
authors.lastname: Simon
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D045744:Cell Line, Tumor; D002952:Citric Acid Cycle; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005978:Glutathione / Q000096:biosynthesis; D006019:Glycolysis; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013217:Starvation / Q000378:metabolism*; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D005978:Glutathione
keywords: autophagy; liver; metabolism; p73; starvation