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. Most importantly, p53 functions to cause arrest of cells in the G1 phase of the cell cycle following any exposure of cells to DNA-damaging agents. The MDM2 (murine double minute-2) protein was initially identified as an oncogene in a murine transformation system. 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. Another p53 target protein is the p53-inducible RING finger protein (p53RFP), an auto-ubiquitinylated protein acting as an E3 ubiquitin ligase. p53RFP, also designated IBRDC2 in mouse and rat, receives ubiquitin from specific E2 ubiquitin-conjugating enzymes and transfers it to substrates that promote their degradation by the proteasome. p53RFP may mediate re-entry into the cell cycle.
