title: Cotranslation of activated mutant p53 with wild type drives the wild-type p53 protein into the mutant conformation.
abstract: Activating mutations of p53 promote tumor progression. The mutant protein adopts a characteristic conformation, which lacks the growth suppressor function of wild-type p53. We show that mutant p53 can drive cotranslated wild-type p53 into the mutant conformation: a similar effect in vivo would block wild-type suppressor function with dominant negative effect. The cotranslational effect of mutant p53 on wild-type conformation depends upon interaction between nascent polypeptides and oligomerization of the full-length proteins. We also show that oligomers of p53 proteins can be induced to change conformation in a cooperative manner. Cell growth stimulation induces a similar conformational change in p53, and our present results indicate that this may involve allosteric regulation.
authors.affiliation: Department of Pathology, University of Cambridge, England.
authors.forename: J
authors.initials: J
authors.lastname: Milner
authors.forename: E A
authors.initials: EA
authors.lastname: Medcalf
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D003001:Cloning, Molecular; D003062:Codon; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D016297:Mutagenesis, Site-Directed; D010957:Plasmids; D014176:Protein Biosynthesis; D011487:Protein Conformation; D013816:Thermodynamics; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D003062:Codon; D016159:Tumor Suppressor Protein p53