MDMX Inhibits the p300/CBP-Mediated Acetylation of p53

Abstract

The p300/CBP-mediated acetylation of p53 significantly potentiates p53-mediated transactivation and growth inhibition. MDM2 inhibits the acetylation of p53 by p300/CBP through a mechanism that requires a stable p53-MDM2 interaction and that is sensitive to the deacetylase inhibitor, TSA. MDMX is an MDM2-like protein that shares with MDM2 the ability to interact with p53 and, in turn, inhibit p53-mediated transcription. It was therefore of interest to determine if MDMX could also inhibit the acetylation of p53 by p300/CBP. We demonstrate that MDMX dramatically inhibits the acetylation of p53 induced by both endogenous and ectopically expressed p300/CBP. We also demonstrate that the p53-binding domain of MDMX is required for the MDMX-mediated inhibition of p53 acetylation. Our results indicate that MDMX shares with MDM2 the ability to regulate a potentially important post-translational modification of p53. These results may have important biologic implications with respect to the MDMX-mediated regulation of p53 activity during development.