Identification of p53 as a sequence-specific DNA-binding protein
@article{Kern1991IdentificationOP, title={Identification of p53 as a sequence-specific DNA-binding protein}, author={Sebastian Kern and K W Kinzler and Arthur M. Bruskin and D Jarosz and Paula N. Friedman and Carol Prives and Bert Vogelstein}, journal={Science}, year={1991}, volume={252}, pages={1708 - 1711} }
The tumor-suppressor gene p53 is altered by missense mutation in numerous human malignancies. However, the biochemical properties of p53 and the effect of mutation on these properties are unclear. A human DNA sequence was identified that binds specifically to wild-type human p53 protein in vitro. As few as 33 base pairs were sufficient to confer specific binding. Certain guanines within this 33-base pair region were critical, as methylation of these guanines or their substitution with thymine…
1,049 Citations
Analysis of a protein-binding domain of p53
- Biology, Chemistry
- 1993
T-antigen binding was unaffected by tumor-derived mutations which have been associated with the wild-type conformation of p53 but was greatly reduced by mutations which were previously shown to alter p53 conformation.
Analysis of a protein-binding domain of p53.
- Biology, ChemistryMolecular and cellular biology
- 1993
T-antigen binding was unaffected by tumor-derived mutations which have been associated with the wild-type conformation of p53 but was greatly reduced by mutations which were previously shown to alter p53 conformation.
Identification of a minimal transforming domain of p53: negative dominance through abrogation of sequence-specific DNA binding.
- BiologyMolecular and cellular biology
- 1992
Mutations in the p53 gene are most frequent in cancer. Many p53 mutants possess transforming activity in vitro. In cells transformed by such mutants, the mutant protein is oligomerized with…
Identification of a minimal transforming domain of p53: negative dominance through abrogation of sequence-specific DNA binding
- Biology
- 1992
Mutations in the p53 gene are most frequent in cancer. Many p53 mutants possess transforming activity in vitro. In cells transformed by such mutants, the mutant protein is oligomerized with…
Sequence-specific interaction of a conformational domain of p53 with DNA.
- Biology, ChemistryCancer research
- 1993
Results demonstrate that DNA-binding activity resides in the conformational domain of p53, providing a structural model for disruption of DNA binding by mutation and suggesting metal ions may regulate binding of p 53 to DNA by modulating its conformation.
Specific recognition of a transcriptional element within the human h-ras protooncogene by the p53 tumor-suppressor.
- BiologyInternational journal of oncology
- 1995
This work has determined that the human c-H-ras gene contains within its first intron sequences that partially match the p53 consensus binding site, and determined that these sequences represent a bona fide p53 element, since in vitro translated wild-type p53 recognized them with high affinity.
Definition of a consensus binding site for p53
- BiologyNature Genetics
- 1992
Recent experiments have suggested that p53 action may be mediated through its inter action with DNA. We have now identified 18 human genomic clones that bind to p53 in vitro. Precise mapping of the…
Oncogenic forms of p53 inhibit p53-regulated gene expression.
- BiologyScience
- 1992
C Cotransfection experiments showed that wild-type p53 activated the expression of genes adjacent to a p53 DNA binding site, which correlated with DNA binding in vitro and provided a basis for the selection of such mutants during tumorigenesis.
Oncogenic forms of p53 inhibit p53-regulated gene expression
- Biology
- 1992
C Cotransfection experiments showed that wild-type p53 activated the expression of genes adjacent to a p53 DNA binding site, which correlated with DNA binding in vitro and provided a basis for the selection of such mutants during tumorigenesis.
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