Stabilization and Activation of p53 by the Coactivator Protein TAF _II31

Regulation of the stability of p53 is key to its tumor-suppressing activities. mdm2 directly binds to the amino-terminal region of p53 and targets it for degradation through the ubiquitin-proteasome pathway. The coactivator protein TAF_II31 binds to p53 at the amino-terminal region that is also required for interaction with mdm2. In this report, we demonstrate that expression of TAF_II31 inhibits mdm2-mediated ubiquitination of p53 and increases p53 levels. TAF_II31-mediated p53 stabilization results in activation of p53-mediated transcriptional activity and leads to p53-dependent growth arrest in fibroblasts. UV-induced stabilization of p53 coincides with an increase in p53-associated TAF_II31 and a corresponding decrease in mdm2-p53 interaction. Non-p53 binding mutant of TAF_II31 fails to stabilize p53. Our results suggest that direct interaction of TAF_II31 and p53 not only mediates p53 transcriptional activation but also protects p53 from mdm2-mediated degradation, thereby resulting in activation of p53 functions.