MDM2 and MDMX bind and stabilize the p53-related protein p73

Journal article

The p53 gene encodes one of the most important tumor suppressors in human cells and undergoes frequent mutational inactivation in cancers. MDM2, a transcriptional target of p53, binds p53 and can both inhibit p53-mediated transcription [1], [2] and target p53 for proteasome-mediated proteolysis [3], [4]. A close relative of p53, p73, has recently been identified [5], [6]. Here, we report that, like p53, p73α and the alternative transcription product p73β also bind MDM2. Interaction between MDM2 and p53 represents a key step in the regulation of p53, as MDM2 promotes the degradation of p53. In striking contrast to p53, the half-life of p73 was found to be increased by binding to MDM2. Like MDM2, the MDM2-related protein MDMX also bound p73 and stabilized the level of p73. Moreover, the growth suppression functions of p73 and the induction of endogenous p21, a major mediator of the p53-dependent growth arrest pathway, were enhanced in the presence of MDM2. These differences between the regulation of p53 and p73 by MDM2/MDMX may highlight a physiological difference in their action.

Authors: Ongkeko, W; Wang, X; Siu, W; Cox, L; al., E

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Current biology : CB
• Volume: 9
• Issue: 15
• Pages: 829-832
• Publication date: 1999-07-01
• Acceptance date: 1999-06-23
• DOI: 10.1016/S0960-9822(99)80367-4
• EISSN: 1879-0445
• ISSN: 0960-9822
• Pmid: 10469568
• Language: English
• Keywords: SBTMR