Identification of partial loss of function p53 gene mutations utilizing a yeast-based functional assay.
Missense mutations within the central DNA binding region of p53 are the most prevalent mutations found in human cancer. Numerous studies indicate that 'hot-spot' p53 mutants (which comprise approximately 30% of human p53 gene mutations) are largely devoid of transcriptional activity. However, a growing body of evidence indicates that some non-hot-spot p53 mutants retain some degree of transcriptional activity in vivo, particularly against strong p53 binding sites. We have modified a previously described yeast-based p53 functional assay to readily identify such partial loss of function p53 mutants. We demonstrate the utility of this modified p53 functional assay using a diverse panel of p53 mutants.
Departments of Medicine and Biochemistry, Robert Wood Johnson Medical School and The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08901, USA.
G K
GK
Kovvali
B
B
Mehta
C B
CB
Epstein
S G
SG
Lutzker
D001483:Base Sequence; D001665:Binding Sites; D002455:Cell Division / Q000235:genetics; D006801:Humans; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D012689:Sequence Homology, Nucleic Acid; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000502:physiology; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D001616:beta-Galactosidase