The MDM2 protein is the primary regulator of p53 protein stability. MDMX is an MDM2-related protein that inhibits MDM2-mediated degradation of p53 via distinct associations with MDM2. The gene that encodes MDMX (also designated MDM4) is a target for amplification in malignant gliomas. ARF interacts with MDMX to sequester MDMX within the nucleolus. This sequestration of MDMX by ARF results in an increase in p53 transactivation. In addition, expression of MDMX can reverse MDM2-targeted degradation of p53 while maintaining suppression of p53 transactivation. Like MDM2, MDMX also binds p73 and stabilizes the level of p73. Therefore, in striking contrast to p53, the half-life of p73 is increased by binding to MDM2.
