p53 is a transcriptional enhancer of a number of DNA damage and growth arrest genes including mdm2, Gadd 45 and WAFI/CIPI, the latter involved in the G1/S phase checkpoint. When expressed at high levels, p53 suppresses transformation, arrests cells in G1 phase and in some cases promotes apoptosis. We have shown that ectopic overexpression of wild-type p53 blocks cell cycle progression near the restriction point late in G1. The G1 arrest is accompanied by down regulation of B-myb, which is thought to promote entry in S-phase. Overexpression of B-myb transgene rescues cells from p53-induced G1 arrest. The ability of wild-type p53 protein to exert an antiproliferative effect correlates with the presence of a unique structure and increased phosphorylation. Since the DNA binding and transactivation functions of p53 are linked to its oligomerization properties, we have defined, by using sedimentation equilibrium ultracentrifugation, the segment of p53 essential to the formation of tetramers. The three-dimensional structure of the core tetramerization domain was determined by high resolution multidimensional NMR techniques. The structure is a dimer of dimers, with the apposing dimers held together principally through interactions between the a-helices. Recent structural studies of the minimal core binding domain of p53 complexed to a single consensus pentamer sequence have provided new insights into the DNA binding mechanism of p53. In a recent study we have shown that the core p53 DNA binding domain, in the absence of the tetramerization domain, binds tightly and cooperatively as a tetrapeptide to several naturally occurring DNA response elements and bends the DNA through a minimum angle of 60 degrees. This demonstrates that the DNA conformation is an important aspect of the binding specificity of this protein.