MDM2 and cancer: p53 is a transcription factor that is distributed in the nucleus and cytoplasm, binds specifically to DNA, and regulates a diversity of genes.25,26 Under normal conditions, cellular p53 protein levels are very low owing to strict control by its negative regulators MDM2 and MDMX, which promote p53 degradation through ubiquitination.27,28 When cells are exposed to internal and external stresses, including DNA damage, hypoxia, nutrient deprivation, and cancer cell risk, p53 ubiquitination is inhibited, triggering a rapid increase in intracellular p53 protein levels.