THE DNA-BINDING DOMAIN OF P53 CONTAINS THE 4 CONSERVED REGIONS AND THE MAJOR MUTATION HOT-SPOTS

Mutations in the p53 tumor suppressor gene are the most commonly obser ved genetic alterations in human cancer. The majority of these mutatio ns occur in the conserved central portion of the gene, but there has b een little information about the function of this region. Using proteo lytic digestion of the 393-amino-acid human p53 protein, we have ident ified a 191-amino-acid protease-resistant fragment (residues 102-292) that corresponds to the central portion of p53, and we show that this core fragment is the sequence-specific DNA-binding domain of the prote in. DNA binding is inhibited by metal chelating agents, and we find th at the core domain contains zinc. Proteolytic digests also reveal a 53 -amino-acid carboxy-terminal domain which we show to be the tetrameriz ation domain of p53.