MDM2 gene encodes a nuclear-localized E3 ubiquitin ligase. The encoded protein can promote tumor formation by targeting tumor suppressor proteins, such as p53, for proteasomal degradation. p53 is the most commonly mutated gene in human cancer identified to date. Expression of p53 leads to inhibition of cell growth by preventing progression of cells from G1 to S phase of the cell cycle. MDM2 functions to bind p53 and block p53-mediated transactivation of cotransfected reporter constructs. The MDM2 gene is amplified in a high percentage of human sarcomas that retain wildtype p53 and tumor cells that overexpress MDM2 can tolerate high levels of p53 expression.
