Oligomerization is required for p53 to be efficiently ubiquitinated by MDM2

Wild-type p53 is degraded in part through the ubiquitin proteolysis pathway . Recent studies indicate that MDM2 can bind p53 and promote its rapid degr adation although the molecular basis for this degradation has not been clar ified. This report demonstrates that MDM2 can promote the ubiquitination of wild-type p53 and cancer-derived p53 mutants in transiently transfected ce lls. Deletion mutants that disrupted the oligomerization domain of p53 disp layed low binding affinity for MDM2 and were poor substrates for ubiquitina tion. However, efficient MDM2 binding and ubiquitination were restored when an olgomerization-deficient p53 mutant was fused to the dimerization domai n from another protein. These results indicate that oligomerization is requ ired for p53 to efficiently bind and be ubiquitinated by MDM2. p53 ubiquiti nation was inhibited in cells exposed to UV radiation, and this inhibition coincided with a decrease in MDM2 protein levels and p53 MDM2 complex forma tion. In contrast, p53 dimerization was unaffected following UV treatment. These results suggest that UV radiation may stabilize p53 by blocking the u biquitination and degradation of p53 mediated by MDM2.