Mdm2 and MdmX: Partners in p53 Destruction

Abstract Mdm2 and MdmX are two closely related proteins that have been well-characterized as negative regulators of the tumor suppressor p53. Their interplay especially respective roles in ubiquitination subsequent degradation p53 lacked clarity. Yang colleagues now demonstrate an obligate role for recruitment E2 ubiquitin ligase UbcH5c to Mdm2-MdmX hetero-oligomer. The use elegant genetically engineered mouse models ensures biological relevance their findings important implications targeted therapies involving these key players pathway. See article by et al., Cancer Res 2021;81:898–909.