Abstract
The p73 protein, a homologue of the tumour-suppressor protein p53, can activate p53-responsive promoters and induce apoptosis in p53-deficient cells. Here we report that some tumour-derived p53 mutants can bind to and inactivate p73. The binding of such mutants is influenced by whether TP53 (encoding p53) codon 72, by virtue of a common polymorphism in the human population, encodes Arg or Pro. The ability of mutant p53 to bind p73, neutralize p73-induced apoptosis and transform cells in cooperation with EJ-Ras was enhanced when codon 72 encoded Arg. We found that the Arg-containing allele was preferentially mutated and retained in squamous cell tumours arising in Arg/Pro germline heterozygotes. Thus, inactivation of p53 family members may contribute to the biological properties of a subset of p53 mutants, and a polymorphic residue within p53 affects mutant behaviour.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Alleles
-
Arginine / genetics
-
Carcinoma, Squamous Cell / genetics
-
Cell Line
-
Codon / genetics
-
DNA-Binding Proteins / antagonists & inhibitors
-
DNA-Binding Proteins / metabolism
-
DNA-Binding Proteins / physiology
-
Genes, Tumor Suppressor
-
Genes, p53
-
Genetic Carrier Screening
-
Germ-Line Mutation
-
Humans
-
Macromolecular Substances
-
Mutagenesis, Site-Directed*
-
Nuclear Proteins / antagonists & inhibitors
-
Nuclear Proteins / metabolism
-
Nuclear Proteins / physiology
-
Polymorphism, Genetic*
-
Proline / genetics
-
Protein Binding / genetics
-
Protein Conformation
-
Tumor Cells, Cultured
-
Tumor Protein p73
-
Tumor Suppressor Protein p53 / genetics*
-
Tumor Suppressor Protein p53 / metabolism*
-
Tumor Suppressor Protein p53 / physiology
-
Tumor Suppressor Proteins
Substances
-
Codon
-
DNA-Binding Proteins
-
Macromolecular Substances
-
Nuclear Proteins
-
TP73 protein, human
-
Tumor Protein p73
-
Tumor Suppressor Protein p53
-
Tumor Suppressor Proteins
-
Arginine
-
Proline