Equal transcription of wild-type and mutant p53 using bicistronic vectors results in the wild-type phenotype.
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.
Frebourg
T
T
Division of Molecular Genetics, Massachusetts General Hospital Cancer Center, Charlestown 02129.
Sadelain
M
M
Ng
Y S
YS
Kassel
J
J
Friend
S H
SH
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