p53: Technical Overview
p53 is a tumor suppressor phosphoprotein that is present at low concentrations in normal cells. The low concentration is maintained by MDM2-mediated ubiquitination and resulting proteolysis. HAUSP/USP7, a newly identified ubiquitin hydrolase, is thought to regulate MDM2 and help stabilize p53. When cells are subjected to stress, such as hypoxia or UV radiation, p53 is activated, its protein levels are elevated and its ubiquitin-dependent degradation is blocked. The resulting increase in p53 leads either to the induction of cell cycle arrest or apoptosis. Cell cycle arrest allows DNA repair to proceed before mitosis. If the damage is severe, p53 activation results in apoptosis. Hence, functional p53 provides a protective effect against tumor growth. Mutations in the p53 gene are commonly seen in various types of human cancers. Any successful response to chemo- or radiation therapy is reduced in tumors containing mutant forms of p53. While significant progress has been made in our understanding of the regulation and activation of p53, the role of post-translational modifications and the precise control of the interaction among p53, HAUSP, and MDM2 remains to be elucidated.