title: Functional studies of a germ-line polymorphism at codon 47 within the p53 gene.
abstract: A rare germ-line polymorphism in codon 47 of the p53 gene replaces the wild-type proline (CCG) with a serine (TCG). Restriction analysis of 101 human samples revealed the frequency of the rare allele to be 0% (n = 69) in Caucasians and 4.7% (3/64, n = 32) among African-Americans. To investigate the consequence of this amino acid substitution, a cDNA construct (p53 mut47ser) containing the mutation was introduced into a lung adenocarcinoma cell line (Calu-6) that does not express p53. A growth suppression similar to that obtained after introduction of a wild-type p53 cDNA construct was observed, in contrast to the result obtained by introduction of p53 mut143ala. Furthermore, expression of neither p53 mut47ser nor wild-type p53 was tolerated by growing cells. In transient expression assays, both mut47ser and wild-type p53 activated the expression of a reporter gene linked to a p53 binding sequence (PG13-CAT) and inhibited the expression of the luciferase gene under the control of the Rous sarcoma virus promoter (RSVluc). In the same assay, mut143ala did not activate the expression of PG13-CAT and produced only a slight inhibitory effect on RSVluc. These findings indicate that the p53 variant with a serine at codon 47 should be considered as a rare germ-line polymorphism that does not alter the growth-suppression activity of p53.
authors.affiliation: Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892.
authors.forename: E
authors.initials: E
authors.lastname: Felley-Bosco
authors.forename: A
authors.initials: A
authors.lastname: Weston
authors.forename: H M
authors.initials: HM
authors.lastname: Cawley
authors.forename: W P
authors.initials: WP
authors.lastname: Bennett
authors.forename: C C
authors.initials: CC
authors.lastname: Harris
mesh_terms: D000483:Alleles; D001483:Base Sequence; D044383:Black People / Q000235:genetics; D003001:Cloning, Molecular; D005787:Gene Frequency; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011392:Proline / Q000235:genetics; D012694:Serine / Q000235:genetics; D013329:Structure-Activity Relationship; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D014481:United States; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: D016159:Tumor Suppressor Protein p53; D012694:Serine; D011392:Proline