The murine double minute 2 (MDM2) is a protein encoded by the mdm2 gene that functions as an E3 ubiquitin ligase to ubiquitinate the p53 tumor suppressor and promotes the proteasomal degradation of p53. Human MDM2 protein is a phosphoprotein of 491 amino acids that inherits the E3 ubiquitin ligase activity from its evolutionarily conserved COOH terminal of RING finger domain (Zinc-binding), a common motif in E3 ligases. Human MDM2 protein mediates monomeric ubiquitination on multiple lysine residues mainly in the COOH terminus of p53 and directly inhibits the transcriptional activity of p53 through binding to the NH2 terminal transactivation domain of p53.