Stimulation of polyomavirus DNA replication by wild-type p53 through the DNA-binding site.
The tumor suppressor p53 possesses characteristics of a transcription factor; it binds to specific DNA sequences and activates transcription from various promoters. Here we found that murine wild-type p53 stimulated not only transcription but also polyomavirus (Py) DNA replication in a sequence-dependent manner. Oncogenic mutant p53, lacking the DNA-binding activity, showed no stimulation of Py DNA replication. Deletion of the N-terminal acidic transactivation domain of wild-type p53, which completely eliminated the ability to stimulate transcription, only impaired the function to stimulate Py DNA replication. The replication-stimulating activity of wild-type p53 was impaired by the deletion of the C-terminal oligomerization domain as well, without affecting the ability to stimulate transcription. The region responsible for the sequence-specific DNA-binding activity mapped to the central portion of the p53 molecule has a minimal activity. The results indicate that both the N-terminal and the C-terminal regions significantly contribute to the p53-mediated stimulation of Py DNA replication.
Kanda
T
T
Department of Viral Oncology, Kyoto University, Japan.
Segawa
K
K
Ohuchi
N
N
Mori
S
S
Ito
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000378:metabolism; D017124:Conserved Sequence; D004261:DNA Replication / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D016158:Genes, p53; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010957:Plasmids; D017354:Point Mutation; D011120:Polyomavirus / Q000235:genetics*; D011401:Promoter Regions, Genetic; D015183:Restriction Mapping; D017384:Sequence Deletion; D013724:Teratoma; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000378:metabolism*
D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D016159:Tumor Suppressor Protein p53; D015500:Chloramphenicol O-Acetyltransferase