Regulation of glucose metabolism by p53: Emerging new roles for the tumor suppressor
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1 Department of Biochemistry, Chhatrapati Shahuji Maharaj Medical University, Lucknow, India
2 Transcription and Human Biology Laboratory, School of Biotechnology, Jawaharlal Nehru University, New-Delhi, India
3 Department of Radiotherapy and Chemotherapy, Chhatrapati Shahuji Maharaj Medical University, Lucknow, India
4 Dorothy M Davis Heart and Lung Research institute, Department of Internal Medicine, Ohio State University, Columbus, Ohio, USA
Received: December 19, 2011; Accepted: December 20, 2011; Published: December 31, 2011;
Keywords: p53, Metabolism, TIGAR, SCO2, Tumor Suppressor
Abbas Ali Mahdi, email:
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.
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