Definition of a consensus binding site for p53
Abstract
Recent experiments have suggested that p53 action may be mediated through its interaction with DNA. We have now identified 18 human genomic clones that bind to p53 in vitro. Precise mapping of the binding sequences within these clones revealed a consensus binding site with a striking internal symmetry, consisting of two copies of the 10 base pair motif 5'-PuPuPuC(A/T)(T/A)GPyPyPy-3' separated by 0-13 base pairs. One copy of the motif was insufficient for binding, and subtle alterations of the motif, even when present in multiple copies, resulted in loss of affinity for p53. Mutants of p53, representing each of the four "hot spots" frequently altered in human cancers, failed to bind to the consensus dimer. These results define the DNA sequence elements with which p53 interacts in vitro and which may be important for p53 action in vivo.
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Typically, p53 binds to target genes as a tetramer comprising two dimers, each binding a decameric half-site with the consensus sequence RRRCWWGYYY.
“Typically, p53 binds to the target genes as a tetramer, which comprises two dimers that each binds a decameric half-site with the consensus sequence RRRCWWGYYY (R = A/G, W = A/T, Y = C/T).7, 8, 9, 10”
From Census and evaluation of p53 target genes (2017) · cites this paper as [7]
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References 20 · Cited by 1,985
- Authors
- El-Deiry, W. S., Kern, S. E., Pietenpol, J. A., Kinzler, K. W., & Vogelstein, B.
- Affiliations
- Johns Hopkins University (US)
- Venue
- Nature Genetics
- Published
- 1992-04
- Volume
- 1
- Issue
- 1
- Pages
- 45-49
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2074222004
- Cited by
- 1,985
- References
- 20
- Citations by year
- 2026: 17 · 2025: 16 · 2024: 23 · 2023: 38 · 2022: 34 · 2021: 29 · 2020: 30 · 2019: 32 · 2018: 46 · 2017: 50 · 2016: 45 · 2015: 40 · 2014: 49 · 2013: 66 · 2012: 60
- FWCI
- 33.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- p53, consensus binding site, DNA-binding motifs, mutant p53, cancer mutations
- MeSH terms
- Base Sequence, Binding Sites, Cloning, Molecular, DNA, Humans, Molecular Sequence Data, Mutation, Protein Binding, Polymerase Chain Reaction, Tumor Suppressor Protein p53, Consensus Sequence
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