p53 Regulation of Metabolic Pathways

During the course of tumorigenesis, cells acquire a number of alterations that contribute to the acquisition of the malignant phenotype, allowing them to survive and flourish in increasingly hostile environments. Cancer cells can be characterized by perturbations in the control of cell proliferation and growth, resistance to death, and alterations in their interactions with the microenvironment. Underpinning many of these changes are shifts in metabolism that allow cancer cells to use alternative pathways for energy production and building the macromolecules necessary for growth, as well as regulating the generation of signaling molecules such as reactive oxygen species (ROS). In the past few years, it became clear that p53, the most studied, if not most important, tumor suppressor protein, can also directly control metabolic traits of cells.Given the importance of metabolic reprogramming in tumor development, it is no surprise that many oncogenes and tumor suppressor genes have been shown to help control these pathways (DeBerardinis et al. 2008a; Tennant et al. 2009). In most cases, these effects are fairly clear—proteins that can promote cancer development drive the metabolic transformation associated with malignancies and tumor suppressor proteins oppose these effects. p53 plays a central and key role in preventing cancer development (Vousden and Prives 2009), but the regulation of metabolism by p53 is proving to be far from straightforward. Although the explanation for this complexity is not clear, there are several obvious and ultimately testable models. What is evident, however, is that the regulation of metabolic pathways is an important facet of p53 function that may provide us with some novel and effective new therapeutic targets, for cancer and maybe also other diseases.