Quantitative analysis of residual folding and DNA binding in mutant p53 core domain: definition of mutant states for rescue in cancer therapy.

Journal article

The tumour suppressor p53 is mutated in half of all human cancers, most frequently with missense substitutions in its core domain. We present a new assessment of the mutation database based on quantitative folding and DNA-binding studies of the isolated core domain. Our data identify five distinct mutant classes that correlate with four well-defined regions of the core domain structure. On extrapolation to 37 degrees C the wild-type protein has a stability of 3.0 kcal/mol. This also emerges a...

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Authors: Bullock, A; Henckel, J; Fersht, A

• Journal: Oncogene
• Volume: 19
• Issue: 10
• Pages: 1245-1256
• Publication date: 2000-03-01
• DOI: 10.1038/sj.onc.1203434
• EISSN: 1476-5594
• ISSN: 0950-9232
• Language: English
• Keywords: Models, Chemical; Tumor Suppressor Protein p53; Models, Molecular; Genes, p53; Recombinant Proteins; Transcriptional Activation; Spectrometry, Fluorescence; Temperature; Databases, Factual; Mutation; Humans; Protein Denaturation; Apoptosis; Protein Folding; Peptide Fragments; Thermodynamics