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… 
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Analysis of a protein-binding domain of p53
TLDR
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.
TLDR
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.
Regulation of the specific DNA binding function of p53
Identification of a minimal transforming domain of p53: negative dominance through abrogation of sequence-specific DNA binding.
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
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.
TLDR
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.
TLDR
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
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.
TLDR
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
TLDR
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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References

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TLDR
The results suggest common pathways by which these various mutations affect the normal function of p53, including four of the evolutionarily conserved domains that are the known 'hot spots' for p53 mutation.
Presence of a potent transcription activating sequence in the p53 protein.
The p53 gene is frequently mutated in a wide variety of human cancers. However, the role of the wild-type p53 gene in growth control is not known. Hybrid proteins that contain the DNA binding domain…
DNA binding properties of murine p53.
We analysed the in vitro binding of p53 from normal (3T3) and from chemically transformed (Meth A) Balb/c mouse cells to double-stranded (ds-) DNA and to single-stranded (ss-) DNA by DNA-cellulose…
Identification and characterization of a p53 gene mutation in a human osteosarcoma cell line.
TLDR
The molecular cloning and sequencing of the p53 gene from HOS-SL cells are reported, and it is demonstrated that it is in fact mutant, whereas the wild type form of p53 appears to be lost in these cells.
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TLDR
These findings, coupled with the previous demonstration of 17p allele loss in lung cancer, strongly implicate p53 as an anti-oncogene whose disruption is involved in the pathogenesis of human lung cancer.
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TLDR
The protein encoded by the wild-type p53 proto-oncogene has been shown to suppress transformation, whereas certain mutations that alter p53 become transformation competent, and the inability of the p53 mutant proteins to activate transcription may enable them to be transformation competent.
p53 functions as a cell cycle control protein in osteosarcomas.
TLDR
It is shown that overexpression of the gene encoding wild-type p53 blocks the growth of osteosarcoma cells, suggesting that the role of the p53 gene as an antioncogene may be in controlling the cell cycle in a fashion analogous to the check-point control genes in Saccharomyces cerevisiae.
The p53 proto-oncogene can act as a suppressor of transformation
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TLDR
The role of inactivation of the p53 gene in the pathogenesis of lung cancer is supported and the role of intronic point mutation in this process is indicated.
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TLDR
Results imply that as in the murine system, the PAb240 antibody reliably detects a wide variety of p53 mutations and that these mutations have a common effect on the structure of p 53.
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