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Dominant-Negative p53 Mutations Selected in Yeast Hit Cancer Hot Spots
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 s...
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| Published in: | Proceedings of the National Academy of Sciences - PNAS 1996-04, Vol.93 (9), p.4091-4095 |
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| Main Authors: | , , |
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| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-c579t-c5d2113cd2e0028ea132f5a14a8b493e67fca55226ce0a36dfb5cfdf29a563963 |
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| container_end_page | 4095 |
| container_issue | 9 |
| container_start_page | 4091 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 93 |
| creator | Brachmann, Rainer K. Vidal, Marc Boeke, Jef D. |
| description | 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. |
| doi_str_mv | 10.1073/pnas.93.9.4091 |
| format | article |
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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1996-04, Vol.93 (9), p.4091-4095 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_pubmed_primary_8633021 |
| source | JSTOR Archival Journals and Primary Sources Collection; PubMed Central |
| subjects | Alleles Amino Acid Sequence Base Sequence Binding sites Blotting, Western Cancer Cloning, Molecular Codon Codons DNA Genes, Dominant Genes, p53 Genetic mutation Genetics Genotype Humans Molecular Sequence Data Mutation Neoplasms - genetics Phenotype Phenotypes Plasmids Point Mutation Proteins Saccharomyces cerevisiae - genetics Tumor Suppressor Protein p53 - biosynthesis Tumor Suppressor Protein p53 - isolation & purification Yeast Yeasts |
| title | Dominant-Negative p53 Mutations Selected in Yeast Hit Cancer Hot Spots |
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