ArticleProceedings of the National Academy of Sciences of the United States of America2017
Diverse p53/DNA binding modes expand the repertoire of p53 response elements.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 46 citations in OpenAlex.
- p53 regulates the expression of histone modifiers to restrict stemness and maintain differentiated luminal identity in breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
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- The PURB-HOTAIR complex regulates p53-dependent promoter-specific transcriptional activation.Nature structural & molecular biology · 2025Article
- p53 reveals principles of chromatin remodeling and enhancer activation.Nucleic acids research · 2025Article
- p53motifDB: integration of genomic information and tumour suppressor p53 binding motifs.Database : the journal of biological databases and curation · 2025Article
- Navigating the complexity of p53-DNA binding: implications for cancer therapy.Biophysical reviews · 2024Review
- A molecular mechanism for the "digital" response of p53 to stress.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Optimisation of TP53 reporters by systematic dissection of synthetic TP53 response elements.Nucleic acids research · 2023Article
- Structural Basis of Mutation-Dependent p53 Tetramerization Deficiency.International journal of molecular sciences · 2022Article
- Protein of a thousand faces: The tumor-suppressive and oncogenic responses of p53.Frontiers in molecular biosciences · 2022Review
- Adaptive homeostasis and the p53 isoform network.EMBO reports · 2021Review
- The Changes in the p53 Protein across the Animal Kingdom Point to Its Involvement in Longevity.International journal of molecular sciences · 2021Article
- The complex architecture of p53 binding sites.Nucleic acids research · 2021Article
- Distinct mechanisms control genome recognition by p53 at its target genes linked to different cell fates.Nature communications · 2021Article
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- Article
- Single molecule studies reveal that p53 tetramers dynamically bind response elements containing one or two half sites.Scientific reports · 2020Article
- The Status of p53 Oligomeric and Aggregation States in Cancer.Biomolecules · 2020Review
- Oncogenic Gain of Function in Glioblastoma Is Linked to Mutant p53 Amyloid Oligomers.iScience · 2020Article
- The Influence of Quadruplex Structure in Proximity to P53 Target Sequences on the Transactivation Potential of P53 Alpha Isoforms.International journal of molecular sciences · 2019Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tumor suppressor protein p53 acts as a transcription factor, binding sequence-specifically to defined DNA sites, thereby activating the expression of genes leading to diverse cellular outcomes. Canonical p53 response elements (REs) are made of two decameric half-sites separated by a variable number of base pairs (spacers). Fifty percent of all validated p53 REs contain spacers between 1 and 18 bp; however, their functional significance is unclear at present. Here, we show that p53 forms two different tetrameric complexes with consensus or natural REs, both with long spacers: a fully specific complex where two p53 dimers bind to two specific half-sites, and a hemispecific complex where one dimer binds to a specific half-site and the second binds to an adjacent spacer sequence. The two types of complexes have comparable binding affinity and specificity, as judged from binding competition against bulk genomic DNA. Structural analysis of the p53 REs in solution shows that these sites are not bent in both their free and p53-bound states when the two half-sites are either abutting or separated by spacers. Cell-based assay supports the physiological relevance of our findings. We propose that p53 REs with long spacers comprise separate specific half-sites that can lead to several different tetrameric complexes. This finding expands the universe of p53 binding sites and demonstrates that even isolated p53 half-sites can form tetrameric complexes. Moreover, it explains the manner in which p53 binds to clusters of more than one canonical binding site, common in many natural REs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.