The p53 tumor-suppressor gene integrates numerous signals that control cell life and death; loss of its functions contributes to the development of most cancers. Recent studies have demonstrated the ability of p53 to regulate the expression of several proteins involved in glycolysis and oxidative phosphorylation, such as TIGAR, SCO2, and phosphoglycerate mutase. TIGAR is a recently discovered protein that functions to regulate glycolysis and protect cells against oxidative stress. TIGAR is similar in structure to proteins in the phosphoglycerate mutase family, most notably 6-phosphofructo-2-kinase, suggesting TIGAR may function as a fructose bisphosphatase. Expression of TIGAR in transfected cells correlated with an inhibition of glycolysis and decreased levels of reactive oxygen species and p53-induced apoptosis, indicating that TIGAR may act to modulate the apoptotic response to p53, thereby allowing cells to survive mild or transient stresses.
