A common polymorphism acts as an intragenic modifier of mutant p53 behaviour

Maria Carmen Marin, Christine A. Jost, Louise A. Brooks, Meredith S. Irwin, Jenny O'Nions, John A. Tidy, Nick James, Jane M. McGregor, Catherine A. Harwood, Isik G. Yulug, Karen H. Vousden, Martin J. Allday, Barry Gusterson, Shuntaro Ikawa, Philip W. Hinds, Tim Crook, William G. Kaelin

研究成果: Article査読

462 被引用数 (Scopus)


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.

ジャーナルNature Genetics
出版ステータスPublished - 2000 5月

ASJC Scopus subject areas

  • 遺伝学


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