Allosteric activation of latent p53 tetramers

The DNA-binding activity of p53 is essential to its function as a tumour suppressor. Point mutations that abolish this activity have been found to occur frequently in the p53 genes of human cancer cells. Wild-type p53 protein assembles into oligomers with latent DNA-binding activity that can be activated in vitro by phosphorylation of a carboxy-terminal regulatory region, catalyzed by protein kinase C or casein kinase II. We have investigated the mechanism underlying this post-translational regulation of p53. Specifically, we have asked the following questions. First, whether the carboxy-terminal regulatory site contributes to p53's ability to form tetramers. Second, whether the latent DNA-binding activity of p53 can be activated in vivo. And third, whether the activation of p53 is reversible.