Functional studies of a germ-line polymorphism at codon 47 within the p53 gene
| Autor: | Emanuela Felley-Bosco, Weston A, Hm, Cawley, Wp, Bennett, Cc, Harris |
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| Rok vydání: | 1993 |
| Předmět: |
Polymorphism
Genetic Base Sequence Proline Molecular Sequence Data Black People Genes p53 Transfection Immunohistochemistry Polymerase Chain Reaction United States White People Structure-Activity Relationship Gene Frequency Mutagenesis Site-Directed Serine Tumor Cells Cultured Humans Point Mutation Cloning Molecular Tumor Suppressor Protein p53 African Continental Ancestry Group/genetics Alleles European Continental Ancestry Group/genetics Genes p53/genetics Proline/genetics Serine/genetics Tumor Suppressor Protein p53/chemistry Tumor Suppressor Protein p53/genetics Research Article |
| Zdroj: | American Journal of Human Genetics, vol. 53, no. 3, pp. 752-759 Scopus-Elsevier Europe PubMed Central |
| ISSN: | 0002-9297 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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