Dominant-negative p53 mutations selected in yeast hit cancer hot spots

Rainer K. Brachmann, Marc Vidal, Jef D. Boeke

    Research output: Contribution to journalArticle

    Abstract

    Clinically important mutant p53 proteins may be tumorigenic through a dominant-negative mechanism or due to a gain-of-function. Examples for both hypotheses have been described; however, it remains unclear to what extent they apply to TP53 mutations in general. Here it is shown that the mutational spectrum of dominant-negative p53 mutants selected in a novel yeast assay correlates tightly with p53 mutations in cancer. Two classes of dominant- negative mutations are described; the more dominant one affects codons that are essential for the stabilization of the DNA-binding surface of the p53 core domain and for the direct interaction of p53 with its DNA binding sites. These results predict that the vast majority of TP53 mutations leading to cancer do so in a dominant-negative fashion.

    Original languageEnglish (US)
    Pages (from-to)4091-4095
    Number of pages5
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume93
    Issue number9
    DOIs
    StatePublished - Apr 30 1996

    ASJC Scopus subject areas

    • General

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