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Istituto di scienza dell'alimentazione

Torna all'elenco Contributi in rivista anno 2002

Contributo in rivista

Tipo: Articolo in rivista

Titolo: Integrating Mutation Data and Structural Analysis of the p53 Tumour-Suppressor Protein

Anno di pubblicazione: 2002

Autori: Martin ACR, Facchiano AM, Cuff AL, Hernandez-Boussard T, Olivier M, Hainaut P, Thornton JM

Affiliazioni autori: A.C.R. Martin: Department of Biochemistry & Molecular Biology, University College London Angelo M. Facchiano: Istituto di Scienze dell'Alimentazione, CNR Avellino T. Hernandez-Boussard, M. Olivier, P.Hainaut: International Agency for Research on Cancer, Lyon, France J.M. Thornton: EBI, Hinxton, UK e Biomolecular Structure and Modelling Unit, Department of Biochemistry and Molecular Biology, University College London, London, UK e Department of Crystallography, Birkbeck College, London, UK

Autori CNR:

  • ANGELO FACCHIANO

Abstract: TP53 encodes p53, which is a nuclear phosphoprotein with cancer-inhibiting properties. In response to DNA damage, p53 is activated and mediates a set of antiproliferative responses including cell-cycle arrest and apoptosis. Mutations in the TP53 gene are associated with more than 50% of human cancers, and 90% of these affect p53-DNA interactions, resulting in a partial or complete loss of transactivation functions. These mutations affect the structural integrity and/or p53-DNA interactions, leading to the partial or complete loss of the protein's function. We report here the results of a systematic automated analysis of the effects of p53 mutations on the structure of the core domain of the protein. We found that 304 of the 882 (34.4%) distinct mutations reported in the core domain can be explained in structural terms by their predicted effects on protein folding or on protein-DNA contacts. The proportion of "explained" mutations increased to 55.6% when substitutions of evolutionary conserved amino acids were included. The automated method of structural analysis developed here may be applied to other frequently mutated gene mutations such as dystrophin, BRCA1, and G6PD.

Pagine da: 149

Pagine a: 164

Rivista:

Human mutation Wiley-Liss,
Paese di pubblicazione: Stati Uniti d'America
Lingua: inglese
ISSN: 1059-7794

Numero volume: 19

Parole chiave:

  • p53
  • structural analysis
  • DNA binding
  • transcription factor
  • relational database

Altre informazioni: 61

Strutture CNR:

 
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