Functional studies of a germ-line polymorphism at codon 47 within the p53 gene

Am J Hum Genet. 1993 Sep;53(3):752-9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*
  • Tumor Suppressor Protein p53 / physiology
  • United States


  • Tumor Suppressor Protein p53
  • Serine
  • Proline