TP53 and cancer: The crucial role of MDM2 in the regulation of p53 activity is supported by the observations that knockout (KO) of the Trp53 gene rescues mouse embryonic lethality caused by Mdm2 loss [6, 7], and that overexpression of MDM2, or its homolog MDMX, frequently occurs in human cancers not harboring TP53 mutations [8].