Article: article from journal or magazin.
Functional studies of a germ-line polymorphism at codon 47 within the p53 gene.
American Journal of Human Genetics
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
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.
African Continental Ancestry Group/genetics, Alleles, Base Sequence, Cloning, Molecular, European Continental Ancestry Group/genetics, Gene Frequency, Genes, p53/genetics, Humans, Immunohistochemistry, Molecular Sequence Data, Mutagenesis, Site-Directed, Point Mutation, Polymerase Chain Reaction, Polymorphism, Genetic, Proline/genetics, Serine/genetics, Structure-Activity Relationship, Transfection, Tumor Cells, Cultured, Tumor Suppressor Protein p53/chemistry, Tumor Suppressor Protein p53/genetics, United States
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