E3 ubiquitin-protein ligase Mdm2 (UniProt Q00987; also known as Double minute 2 protein, Hdm2, Oncoprotein Mdm2, p53-binding protein Mdm2) is encoded by the MDM2 gene (Gene ID 4193) in human. MDM2 is an E3 ubiquitin ligase that is most widely studied for its role in regulating the p53 tumor suppressor. MDM2 antagonizes p53 transcriptional activity by binding to and blocking p53 N-terminal trans-activation domain. MDM2 can also monoubiquitinate p53, thereby promoting p53 cytoplasmic localization to prevent p53 nuclear funtion. In addition, MDM2, when in complex with p300, also mediates p53 polyubiquitination, resulting in p53 proteosomal degradation. MDM2 overexpression is shown to inhibit DNA double-strand break repair mediated through its interaction with Nbs1 in a p53-independent manner.