Suppression of cellular proliferation using p53 DNA recognition site-related oligonucleotides.
A number of oligonucleotides were designed to bind through Hoogsteen triple helix or Watson-Crick hydrogen bonds to the p53 consensus sequence homology localized within the human nontranscribed rRNA spacer region. The oligomers, which bind in vitro to the consensus sequence homology, function as p53 analogues in cells deficient in wild-type p53 protein. Oligomers suppress proliferation of human colon cancer cells by three to eightfold, but only suppress proliferation of normal human mesangial cells or lung fibroblasts by less than 50%. On the basis of these studies, p53 analogues may be used therapeutically to selectively modify proliferation of transformed cells.
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Alton Ochsner Medical Foundation, Division of Research, New Orleans, Louisiana, USA.
Cook
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D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002455:Cell Division; D002460:Cell Line; D016384:Consensus Sequence; D004275:DNA, Ribosomal / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry; D003852:Deoxyribonucleoproteins / Q000737:chemistry; D016158:Genes, p53; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; D003852:Deoxyribonucleoproteins; D009838:Oligodeoxyribonucleotides; D016159:Tumor Suppressor Protein p53