The regulation of energy generating metabolic pathways by p53

The function of p53 as a tumor suppressor remains undisputed. p53 has a central role in cellular stress responses as well as affecting cancer development and progression. The word “central”, however, is becoming increasingly more of an understatement as the list of p53-regulated pathways and processes is ever expanding. Although much focus continues to center on p53-mediated signaling cascades that control cell growth arrest and/or apoptosis, recent work has begun to define a role for p53 in the regulation of metabolic pathways typically thought of as essential for maintaining life. With the first potential link between p53 and glycolysis reported nearly ten years ago, the topic has gained a renewed interest. Recent studies now demonstrate the ability of p53 to regulate the expression of several novel genes including PGM (phosphoglycerate mutase), TIGAR (TP53-induced glycolysis and apoptosis regulator) and, SCO2 (synthesis of cytochrome c oxidase 2), each intimately linked to the processes of glycolysis and oxidative phosphorylation. With this discovery, yet another novel means by which p53 carries out its tumor suppressor function is brought into light.

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