MDM2 and MDMX bind and stabilize the p53-related protein p73
Abstract
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.
- Publication:
-
Current Biology
- Pub Date:
- August 1999
- DOI:
- 10.1016/S0960-9822(99)80367-4
- Bibcode:
- 1999CBio....9..829O