P53 DOMAINS - IDENTIFICATION AND CHARACTERIZATION OF 2 AUTONOMOUS DNA-BINDING REGIONS

We have investigated the DNA-binding, oligomerization, and trans-activ ation functions of isolated segments of murine p53. We find that p53 h as two autonomous DNA-binding regions. One domain, from amino acid 280 to 390, forms stable tetramers and binds DNA nonspecifically. The bio logical significance, if any, of this DNA-binding activity is not know n. A second domain, from amino acid 80 to 290 does not form stable tet ramers under stringent conditions but binds DNA both specifically and nonspecifically. The specific DNA-binding function of p53, therefore, resides in the highly conserved central region of the protein and does not require stable tetramerization. Amino acids 1-290, which include both the specific DNA-binding domain and the amino-terminal acidic reg ion, activate a p53-specific promoter in vivo. This finding strongly a rgues that the DNA-binding activity of p53 segment 80-290 is physiolog ically significant. The role of tetramerization in p53 function remain s to be determined.