UC San Diego

The p53 tumor suppressor protein is an important molecule studied extensively in cancer research. In order to study the mechanism of tumor suppression by p53, structural knowledge is needed. Although the structure of the p53 DNA binding domain bound to DNA has been well elucidated, there is a lack of structural knowledge of the regulatory domain of p53 bound to the DNA. Structural knowledge of this domain bound to the DNA would contribute to the full understanding of the p53 tumor suppression mechanism. In order to solve this problem, X-ray crystallography was used to elucidate the p53 regulatory domain structure. In order to facilitate the crystallization of p53 regulatory domain with DNA, oligomerization of p53 with various DNAs was studied using the sedimentation velocity method. Functional aspects of p53 regulation were studied including acetylation and interaction with the MDM2 protein. It has been found that the p53 regulatory domain binds to both the consensus and non-consensus DNA as a tetramer, and the interaction of the p53 regulatory domain with MDM2 produces a novel MDM2 oligomerization state