The regulation of energy metabolism and the IGF-1/mTOR pathways by the p53 protein

Abstract

In response to stress, p53 initiates the transcriptional regulation of selected target genes and various cellular responses, including cell cycle arrest, apoptosis and senescence. Recent studies revealed two additional functions of p53 in the regulation of IGF-1/AKT/mTOR pathways and energy metabolism, contributing to p53's role as a tumor suppressor. Oncogenic processes give rise to metabolic pathways focused upon the use of aerobic glycolysis (the Warburg effect) and the pentose shunt, providing higher levels of reducing activities. p53 shuts down these pathways and refocuses cells to utilize mitochondrial oxidative phosphorylation, thereby maximizing efficient ATP production and minimizing the synthesis of substrates for cell division. The use of these alternative metabolic pathways is an integral part of both normal and oncogenic phenotypes. © 2010 Elsevier Ltd.