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.

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Howard Hughes Medical Institute


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We thank D. Brash, C. Maki and members of the Kaelin and Crook Laboratory for useful discussions; C. DiComo and C. Prives for sharing their data before publication; A. Fernandez for support and discussions; and L. Billingham and D. Moffit for statistical advice. M.C.M. is funded by an NIH training grant to D.F.C.I., L.A.B. is funded by the Medical Research Coucil, J.O. by the Leukemia Research Fund, M.S.I. is funded by American Cancer Society and I.G.Y. by British Council in Turkey. T.C. is supported by the Leopold Muller Trust and W.G.K. is a Howard Hughes Medical Institute assistant investigator. This work was sponsored in part by the National Cancer Institute, DHHS, under contract with ABL.

Author information


  1. Dana-Farber Cancer Institute and Harvard Medical School , Boston, Massachusetts, USA

    • Maria Carmen Marin
    • , Christine A. Jost
    • , Meredith S. Irwin
    •  & William G. Kaelin Jr
  2. London School of Hygiene and Tropical Medicine, London, UK

    • Louise A. Brooks
    •  & Jenny O'Nions
  3. Section of Cell Biology and Experimental Pathology, Institute of Cancer Research, London, UK

    • Louise A. Brooks
    • , Jenny O'Nions
    • , Isik G. Yulug
    • , Barry Gusterson
    •  & Tim Crook
  4. Department of Gynaecological Oncology, University of Sheffield, Northern General Hospital, Sheffield, UK

    • John A. Tidy
  5. CRC Institute of Cancer Studies, University of Birmingham , Birmingham, UK

    • Nick James
  6. Centre for Cutaneous Research, London, UK

    • Jane M. McGregor
    •  & Catherine A. Harwood
  7. ABL Basic Research Program, National Cancer Institute-Frederick Cancer, Research and Development Center, Frederick, Maryland, USA

    • Karen H. Vousden
  8. Ludwig Institute for Cancer Research, Imperial College of Science, Technology and Medicine, St Mary's Hospital, London , UK

    • Martin J. Allday
  9. Department of Cell Biology, Institute of Development Aging and Cancer, Tohoku University, Sendai, Japan

    • Shuntaro Ikawa
  10. Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA

    • Philip W. Hinds


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