Wild-type but not mutant p53 immunopurified proteins bind to sequences adjacent to the SV40 origin of replication.
The DNA from a wide variety of human tumors has sustained mutations within the conserved p53 coding regions. We have purified wild-type and tumor-derived mutant p53 proteins expressed from baculovirus vectors and examined their interactions with SV40 DNA. Using DNAase I footprinting assays, we observed that both human and murine wild-type p53 proteins bind specifically to sequences adjacent to the late border of the viral replication origin. By contrast, mutant p53 proteins failed to bind specifically to these sequences. SV40 T antigen prevented wild-type p53 from interacting with this region. These data show that normal but not oncogenic forms of p53 are capable of sequence-specific interactions with viral DNA. Furthermore, they provide insights into the mechanisms by which viral proteins might regulate the control of viral growth and cell division.
Bargonetti
J
J
Department of Biological Sciences, Columbia University, New York, New York 10027.
Friedman
P N
PN
Kern
S E
SE
Vogelstein
B
B
Prives
C
C
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004261:DNA Replication; D004279:DNA, Viral / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D066298:In Vitro Techniques; D051379:Mice; D011994:Recombinant Proteins / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D013539:Simian virus 40 / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
D000952:Antigens, Polyomavirus Transforming; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53