title: GAMT joins the p53 network: branching into metabolism.
abstract: The p53 protein functions to prevent tumor development by restricting proliferation, motility and survival of abnormal or stressed cells. In addition to well-established roles, recent discoveries indicate a role for p53 in the regulation of pathways involved in energy metabolism. The metabolic functions of p53 can inhibit the shift to glycolysis that is characteristically seen in cancer cells, while favoring the energy production by mitochondrial oxidative phosphorylation. Identification of guanidinoacetate methyltransferase (GAMT) as a new p53 target connects p53 to creatine metabolism critical in the regulation of ATP homeostasis. The involvement of GAMT in both genotoxic and metabolic stressinduced apoptosis, as well as the requirement of p53-dependent upregulation of GAMT in glucose starvation-mediated fatty acid oxidation (FAO), demonstrate a further role of p53 in coordinating stress response with changes in cellular metabolism. Such activities of p53 would help to bring a better understanding of how cancer cells acquire unique metabolic features to maintain their own survival and proliferation, and might provide interesting clues toward the development of novel therapies.
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
authors.forename: Takao
authors.initials: T
authors.lastname: Ide
authors.forename: Kiki
authors.initials: K
authors.lastname: Chu
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Aaronson
authors.forename: Sam W
authors.initials: SW
authors.lastname: Lee
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D004734:Energy Metabolism; D006019:Glycolysis; D050937:Guanidinoacetate N-Methyltransferase / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation; D009369:Neoplasms / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism* / Q000502:physiology
chemical_list: D016159:Tumor Suppressor Protein p53; D000255:Adenosine Triphosphate; D050937:Guanidinoacetate N-Methyltransferase; D003401:Creatine