Glycolysis links p53 function with NF-kappaB signaling: impact on cancer and aging process.

In 1930, Otto Warburg observed that cancer cells produce an increased amount of their energy through aerobic glycolysis and subsequently, this was called the Warburg effect. During aging, the capacity for mitochondrial respiration clearly declines and aerobic glycolysis appears to compensate for the deficiency in oxidative metabolism. This shift in energy production, both in aging and cancer, could protect from the toxic effects of oxygen free radicals whereas increased glycolysis can have adverse effects. It was recently demonstrated that the glycolysis-linked protein O-glycosylation can potentiate the catalytic activity of IKK beta and subsequently trigger NF-kappaB signaling. It seems that tumor suppressor oncogene p53 has an important role in the regulation of protein O-glycosylation since p53 is a potent inhibitor of glycolysis, for example, via TIGAR protein expression. Aging is known to repress the function of p53 and this could enhance glycolysis and NF-kappaB signaling. We will discuss the role of p53 in the regulation of glycolysis-dependent activation of NF-kappaB signaling in both cancer and aging process. (c) 2010 Wiley-Liss, Inc.