title: Redox modulation of p53 conformation and sequence-specific DNA binding in vitro.
abstract: The p53 protein is a transcription factor, the function of which is abrogated by oncogenic mutations which affect a flexible domain in the central portion of p53, altering its reactivity with conformation-specific antibodies. Here we show that both conformation and sequence-specific DNA binding of p53 translated in vitro can be modulated by metal chelators and oxidizing agents. Oxidation disrupted wild-type p53 conformation and inhibited DNA binding. Conversely, reduction favored folding of p53 into the wild-type form and restored DNA binding. Redox regulation of p53 protein conformation could represent an important mechanism for the control of p53 function.
authors.affiliation: Department of Biology, University of York, Heslington, United Kingdom.
authors.forename: P
authors.initials: P
authors.lastname: Hainaut
authors.forename: J
authors.initials: J
authors.lastname: Milner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001483:Base Sequence; D004247:DNA / Q000378:metabolism*; D003958:Diamide / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000378:metabolism*; D010084:Oxidation-Reduction; D014176:Protein Biosynthesis; D011487:Protein Conformation; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D013816:Thermodynamics; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D003958:Diamide; D004247:DNA; D004229:Dithiothreitol