How p53 binds DNA as a tetramer
Open accessAbstract
The p53 tumor suppressor protein is a tetramer that binds sequence-specifically to a DNA consensus sequence consisting of two consecutive half-sites, with each half-site being formed by two head-to-head quarter-sites (--><-- --><--). Each p53 subunit binds to one quarter-site, resulting in all four DNA quarter-sites being occupied by one p53 tetramer. The tetramerization domain forms a symmetric dimer of dimers, and two contrasting models have the two DNA-binding domains of each dimer bound to either consecutive or alternating quarter-sites. We show here that the two monomers within a dimer bind to a half-site (two consecutive quarter-sites), but not to separated (alternating) quarter-sites. Tetramers bind similarly, with the two dimers within each tetramer binding to pairs of half-sites. Although one dimer within the tetramer is sufficient for binding to one half-site in DNA, concurrent interaction of the second dimer with a second half-site in DNA drastically enhances binding affinity (at least 50-fold). This cooperative dimer-dimer interaction occurs independently of tetramerization and is a primary mechanism responsible for the stabilization of p53 DNA binding. Based on these findings, we present a model of p53 binding to the consensus sequence, with the tetramer binding DNA as a pair of clamps.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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 [8]
Cites
p53, the cellular gatekeeper for growth and division
Levine, A. J. (1997) · Cell · doi:10.1016/s0092-8674(00)81871-1 · Cited by 7,693 · see citing works
Crystal Structure of a p53 Tumor Suppressor-DNA Complex: Understanding Tumorigenic Mutations
Cho, Y., Gorina, S., Jeffrey, P. D., & Pavletich, N. P. (1994) · Science · doi:10.1126/science.8023157 · Cited by 2,559 · cited 9× · see citing works
“…as the primary intra-dimer, inter-monomer interaction in the model of tetramers binding DNA as one dimer binding to quarter-sites one and three, the other dimer binding to sites two and four (Cho et al., 1994; Lee et al., 1994; Jeffrey et al., 1995; Arrowsmith and Morin, 1996; Pennisi, 1996).”
BackgroundMethodInfluentialp53: puzzle and paradigm.Preprint
Ko, L. J., & Prives, C. L. (1996) · Genes & Development · doi:10.1101/gad.10.9.1054 · Cited by 2,338 · see citing works
Definition of a consensus binding site for p53
El-Deiry, W. S., Kern, S. E., Pietenpol, J. A., Kinzler, K. W., & Vogelstein, B. (1992) · Nature Genetics · doi:10.1038/ng0492-45 · Cited by 1,985 · see citing works
Identification of p53 as a Sequence-Specific DNA-Binding Protein
Kern, S. E., Kinzler, K. W., Bruskin, A. M., Jarosz, D., Friedman, P. N., Prives, C. L., & Vogelstein, B. (1991) · Science · doi:10.1126/science.2047879 · Cited by 1,085 · see citing works
A Transcriptionally Active DNA-Binding Site for Human p53 Protein Complexes
Funk, W. D., Pak, D. T. S., Karas, R. H., Wright, W. E., & Shay, J. W. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.6.2866 · Cited by 732 · see citing works
Crystal Structure of the Tetramerization Domain of the p53 Tumor Suppressor at 1.7 Angstroms
Jeffrey, P. D., Gorina, S. S., & Pavletich, N. P. (1995) · Science · doi:10.1126/science.7878469 · Cited by 548 · see citing works
The DNA-binding domain of p53 contains the four conserved regions and the major mutation hot spots.Preprint
Pavletich, N. P., Chambers, K. A., & Pabo, C. O. (1993) · Genes & Development · doi:10.1101/gad.7.12b.2556 · Cited by 521 · see citing works
Somatic point mutations in the p53 gene of human tumors and cell lines: updated compilation
Hollstein, M. (1996) · Nucleic Acids Research · doi:10.1093/nar/24.1.141 · Cited by 499 · see citing works
von Hippel, P. H., & McGhee, J. D. (1972) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.41.070172.001311 · Cited by 407 · see citing works
High-Resolution Structure of the Oligomerization Domain of p53 by Multidimensional NMR
Clore, G. M., Omichinski, J. G., Sakaguchi, K., Zambrano, N., Sakamoto, H., Appella, E., & Gronenborn, A. M. (1994) · Science · doi:10.1126/science.8023159 · Cited by 305 · see citing works
Solution structure of the tetrameric minimum transforming domain of p53
Lee, W., Harvey, T. S., Yin, Y., Yau, P., Litchfield, D. W., & Arrowsmith, C. H. (1994) · Nature Structural & Molecular Biology · doi:10.1038/nsb1294-877 · Cited by 265 · see citing works
p53 domains: identification and characterization of two autonomous DNA-binding regions.Preprint
Wang, Y., Reed, M. J., Wang, P., Stenger, J. E., Mayr, G. A., Anderson, M. E., Schwedes, J. F., & Tegtmeyer, P. (1993) · Genes & Development · doi:10.1101/gad.7.12b.2575 · Cited by 239 · see citing works
A Transcriptionally Active DNA-Binding Site for Human p53 Protein Complexes
Funk, W. D., Pak, D. T. S., Karas, R. H., et al. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.6.2866-2871.1992 · Cited by 239 · see citing works
Refined solution structure of the oligomerization domain of the tumour suppressor p53
Clore, G. M., Ernst, J. A., Clubb, R. T., Omichinski, J. G., Kennedy, W. P., Sakaguchi, K., Appella, E., & Gronenborn, A. M. (1995) · Nature Structural & Molecular Biology · doi:10.1038/nsb0495-321 · Cited by 224 · see citing works
Halazonetis, T. D., & Kandil, A. N. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb06199.x · Cited by 205 · see citing works
Structural Aspects of the p53 Protein in Relation to Gene Evolution: A Second Look
Soussi, T., & May, P. (1996) · Journal of Molecular Biology · doi:10.1006/jmbi.1996.0425 · Cited by 203 · see citing works
p53: a Glimpse at the Puppet Behind the Shadow Play
Friend, S. H. (1994) · Science · doi:10.1126/science.8023155 · Cited by 152 · see citing works
Interaction of p53 with Its Consensus DNA-Binding Site
Wang, Y., Schwedes, J. F., Parks, D., Mann, K., & Tegtmeyer, P. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.4.2157 · Cited by 149 · see citing works
Waterman, J. L. F., Shenk, J. L., & Halazonetis, T. D. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb07027.x · Cited by 126 · see citing works
Four p53 DNA-binding domain peptides bind natural p53-response elements and bend the DNA.
Balagurumoorthy, P., Sakamoto, H., Lewis, M. S., Zambrano, N., Clore, G. M., Gronenborn, A. M., Appella, E., & Harrington, R. E. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.19.8591 · Cited by 126 · see citing works
New insights into p53 function from structural studies.
Arrowsmith, C. H., & Morin, P. J. (1996) · PubMed · Cited by 88 · see citing works
Interhelical Angles in the Solution Structure of the Oligomerization Domain of p53: Correction
Clore, G. M., Omichinski, J. G., Sakaguchi, K., et al. (1995) · Science · doi:10.1126/science.7878474 · Cited by 78 · see citing works
Filling In the Blanks in the p53 Protein Structure
Pennisi, E. (1996) · Science · doi:10.1126/science.274.5289.921 · Cited by 17 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Census and evaluation of p53 target genes
Fischer, M. (2017) · Oncogene · doi:10.1038/onc.2016.502 · Cited by 971 · see citing works
Stommel, J. M., Marchenko, N. D., Jimenez, G. S., Moll, U. M., Hope, T. J., & Wahl, G. M. (1999) · The EMBO Journal · doi:10.1093/emboj/18.6.1660 · Cited by 738 · see citing works
Transcriptional Regulation by P53
Beckerman, R., & Prives, C. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a000935 · Cited by 569 · see citing works
The expanding universe of p53 targets
Menendez, D., Inga, A., & Resnick, M. A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2730 · Cited by 568 · see citing works
Structural Basis of DNA Recognition by p53 Tetramers
Kitayner, M., Rozenberg, H., Kessler, N., Rabinovich, D., Shaulov, L., Haran, T. E., & Shakked, Z. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.05.015 · Cited by 408 · see citing works
Chen, J., & Sadowski, I. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407069102 · Cited by 111 · see citing works
Noncanonical DNA Motifs as Transactivation Targets by Wild Type and Mutant p53
Jordan, J. J., Menendez, D., Inga, A., Nourredine, M., Bell, D., & Resnick, M. A. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000104 · Cited by 103 · see citing works
Yakovlev, V. A., Bayden, A. S., Graves, P. R., Kellogg, G. E., & Mikkelsen, R. B. (2010) · Biochemistry · doi:10.1021/bi100564w · Cited by 56 · see citing works
- Authors
- McLure, K. G., & Lee, P. W. K.
- Affiliations
- University of Calgary (CA)
- Corresponding author
- Lee, Patrick W.K.
- Venue
- The EMBO Journal
- Published
- 1998-06-15
- Volume
- 17
- Issue
- 12
- Pages
- 3342-3350
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1170672
- OpenAlex
- W2095732342
- Cited by
- 260
- References
- 24
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 5 · 2023: 6 · 2022: 9 · 2021: 7 · 2020: 7 · 2019: 9 · 2018: 13 · 2017: 5 · 2016: 5 · 2015: 6 · 2014: 7 · 2013: 9 · 2012: 10
- FWCI
- 5.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- p53, DNA binding, tetramerization domain, cooperative DNA binding, dimer-dimer interactions, tumor suppressor proteins, binding affinity
- MeSH terms
- DNA, DNA-Binding Proteins, Humans, Polymers, Genes, Tumor Suppressor, Tumor Suppressor Protein p53
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
