p53 domains: identification and characterization of two autonomous DNA-binding regions.
We have investigated the DNA-binding, oligomerization, and trans-activation functions of isolated segments of murine p53. We find that p53 has two autonomous DNA-binding regions. One domain, from amino acid 280 to 390, forms stable tetramers and binds DNA nonspecifically. The biological significance, if any, of this DNA-binding activity is not known. A second domain, from amino acid 80 to 290, does not form stable tetramers 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 region, activate a p53-specific promoter in vivo. This finding strongly argues that the DNA-binding activity of p53 segment 80-290 is physiologically significant. The role of tetramerization in p53 function remains to be determined.
Wang
Y
Y
Department of Microbiology, State University of New York, Stony Brook 11794.
Reed
M
M
Wang
P
P
Stenger
J E
JE
Mayr
G
G
Anderson
M E
ME
Schwedes
J F
JF
Tegtmeyer
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002874:Chromosome Mapping; D004247:DNA / Q000378:metabolism; D007313:Insecta; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics* / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D004247:DNA