THE CARBOXYL-TERMINAL DOMAIN OF THE P53 PROTEIN REGULATES SEQUENCE-SPECIFIC DNA-BINDING THROUGH ITS NONSPECIFIC NUCLEIC ACID-BINDING ACTIVITY

The murine p53 protein contains two nucleic acid-binding sites, a sequ ence-specific DNA-binding region localized between amino acid residues 102-290 and a nucleic acid-binding site without sequence specificity that has been localized to residues 364-390, Alternative splicing of m RNA generates two forms of this p53 protein. The normal, or majority, splice form (NSp53) retains its carboxyl-terminal sequence-nonspecific nucleic acid-binding site, which can negatively regulate the sequence -specific DNA-binding site. The alternative splice form of p53 (ASp53) replaces amino acid residues 364-390 with 17 different amino acids. T his protein fails to bind nucleic acids nonspecifically and is constit utive for sequence-specific DNA binding, Thus, the binding of nucleic acids at the carboxyl terminus regulates sequence-specific DNA binding by p53, The implications of these findings for the activation of p53 transcriptional activity following DNA damage are discussed.