p53 mutants with changes in conserved region II: three classes with differing antibody reactivity, SV40 T antigen binding and ability to inhibit transformation of rat cells.
The wild-type p53 gene is able to inhibit the ability of a number of oncogenes to induce transformation, but this inhibition is frequently lost when the p53 gene undergoes mutation. In this study, we generated mutated mouse p53 proteins containing conservative amino acid substitutions at residues 127 to 138 and at 140. The mutant proteins fell into three distinct classes. Class I proteins reacted well with PAb246 (246+), poorly with PAb240 (240-), bound to SV40 T antigen (T+), and inhibited the transformation of rat embryo fibroblasts by adenovirus E1a and activated ras. Class II proteins were 246-, 240+, T-, and failed to inhibit transformation. Class III proteins were 246+, 240-, but T-, and varied in their ability to inhibit transformation. The existence and properties of the Class III proteins suggest that the residues mutated in this class are important for binding to T antigen. They also lead us to conclude that the maintenance of an apparent wild-type structure is not sufficient for p53 to inhibit transformation and that the loss of T antigen binding does not necessarily result in loss of transformation inhibition. We propose the existence of a third activity important for the ability of p53 to inhibit transformation.
School of Life and Health Sciences, University of Delaware, Newark 19716.
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Schmieg
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Simmons
D017500:Adenovirus E1A Proteins / Q000235:genetics; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D017124:Conserved Sequence; D016158:Genes, p53; D011905:Genes, ras; D051379:Mice; D009154:Mutation; D051381:Rats; D013539:Simian virus 40 / Q000276:immunology*; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000494:pharmacology
D017500:Adenovirus E1A Proteins; D000952:Antigens, Polyomavirus Transforming; D016159:Tumor Suppressor Protein p53