title: Regulation of glucose metabolism by p53: emerging new roles for the tumor suppressor.
abstract: p53 is well known as the "guardian of the genome" for differentiated and neoplastic cells. p53 induces cell-cycle arrest and cell death after DNA damage and thus contributes to the maintenance of genomic stability. In addition to this tumor suppressor function for pro-oncogenic cells, p53 also plays an important role as the central regulator of stress response by maintaining cellular homeostasis at the molecular and biochemical level. p53 regulates aerobic respiration at the glycolytic and oxidative phosphorylation (OXPHOS) steps via transcriptional regulation of its downstream genes TP53-induced glycolysis regulator (TIGAR) and synthesis of cytochrome c oxidase (SCO2). p53 negatively regulates glycolysis through activation of TIGAR (an inhibitor of the fructose-2,6-bisphosphate). On the contrary p53 positively regulates OXPHOS through upregulation of SCO2, a member of the COX-2 assembly involved in the electron-transport chain. It is interesting to notice that p53 antagonistically regulates the inter-dependent glycolytic and OXPHOS cycles. It is important to understand whether the p53-mediated transcriptional regulation of TIGAR and SCO2 is temporally segregated in cancer cells and what is the relation between these paradoxical regulations of glycolytic pathway with the tumor suppressor activity of p53. In this review we will elucidate the importance of p53-mediated regulation of glycolysis and OXPHOS and its relation with the tumor suppressor function of p53. Further since cellular metabolism shares great relation with the process of aging we will also try and establish the role of p53 in regulation of aging via its transcriptional control of cellular metabolism.
authors.affiliation: Department of Biochemistry, Chhatrapati Shahuji Maharaj Medical University, Lucknow, India.
authors.forename: Esha
authors.initials: E
authors.lastname: Madan
authors.forename: Rajan
authors.initials: R
authors.lastname: Gogna
authors.forename: Madan
authors.initials: M
authors.lastname: Bhatt
authors.forename: Uttam
authors.initials: U
authors.lastname: Pati
authors.forename: Periannan
authors.initials: P
authors.lastname: Kuppusamy
authors.forename: Abbas Ali
authors.initials: AA
authors.lastname: Mahdi
mesh_terms: D051017:Apoptosis Regulatory Proteins; D059447:Cell Cycle Checkpoints; D019069:Cell Respiration / Q000235:genetics*; D004249:DNA Damage; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics*; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D010085:Oxidative Phosphorylation; D010744:Phosphoric Monoester Hydrolases; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D003576:Electron Transport Complex IV; D010744:Phosphoric Monoester Hydrolases; C512708:TIGAR protein, human; D005947:Glucose