title: Equal transcription of wild-type and mutant p53 using bicistronic vectors results in the wild-type phenotype.
abstract: Somatic and germ-line mutations of p53 alleles inactivate the function of the protein. It has been suggested that mutant p53 can inactivate the wild-type protein and therefore have a trans-dominant negative effect. To investigate the interaction between wild-type and mutant proteins when both alleles are equally transcribed, we designed bicistronic vectors containing the internal ribosome entry site of the encephalomyocarditis virus and expressing wild-type and mutant p53. Analysis of the transcriptional activity and of the effect on cell growth of these plasmids indicates that the mutant protein is unable to completely suppress wild-type function. These results could explain why the inactivation of both p53 alleles is required in cancer development.
authors.affiliation: Division of Molecular Genetics, Massachusetts General Hospital Cancer Center, Charlestown 02129.
authors.forename: T
authors.initials: T
authors.lastname: Frebourg
authors.forename: M
authors.initials: M
authors.lastname: Sadelain
authors.forename: Y S
authors.initials: YS
authors.lastname: Ng
authors.forename: J
authors.initials: J
authors.lastname: Kassel
authors.forename: S H
authors.initials: SH
authors.lastname: Friend
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002478:Cells, Cultured; D016158:Genes, p53; D005822:Genetic Vectors; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D014158:Transcription, Genetic