ArticleNucleic acids research2021
The complex architecture of p53 binding sites.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- NOLC1 suppresses immunochemotherapy by inhibiting p53-mediated ferroptosis in gastric cancer.eLife · 2025Article
- Asymmetry of Motif Conservation Within Their Homotypic Pairs Distinguishes DNA-Binding Domains of Target Transcription Factors in ChIP-Seq Data.International journal of molecular sciences · 2025Article
- Crosstalk between paralogs and isoforms influences p63-dependent regulatory element activity.Nucleic acids research · 2024Article
- Article
- Determinants of p53 DNA binding, gene regulation, and cell fate decisions.Cell death and differentiation · 2024Review
- [Relationship between GTSE1 and Cell Cycle and Potential Regulatory Mechanisms in Lung Cancer Cells].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2024Review
- Context dependent activity of p63-bound gene regulatory elements.bioRxiv : the preprint server for biology · 2024Article
- The presence of a G-quadruplex prone sequence upstream of a minimal promoter increases transcriptional activity in the yeast Saccharomyces cerevisiae.Bioscience reports · 2023Article
- 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
- How Do Cancer-Related Mutations Affect the Oligomerisation State of the p53 Tetramerisation Domain?Current issues in molecular biology · 2023Article
- Sequence Properties of An Intramolecular Interaction That Inhibits p53 DNA Binding.Biomolecules · 2022Article
- Structural Basis of Mutation-Dependent p53 Tetramerization Deficiency.International journal of molecular sciences · 2022Article
- Adaptive homeostasis and the p53 isoform network.EMBO reports · 2021Review
- Structural basis of reactivation of oncogenic p53 mutants by a small molecule: methylene quinuclidinone (MQ).Nature communications · 2021Article
- Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sequence-specific protein-DNA interactions are at the heart of the response of the tumor-suppressor p53 to numerous physiological and stress-related signals. Large variability has been previously reported in p53 binding to and transactivating from p53 response elements (REs) due, at least in part, to changes in direct (base) and indirect (shape) readouts of p53 REs. Here, we dissect p53 REs to decipher the mechanism by which p53 optimizes this highly regulated variable level of interaction with its DNA binding sites. We show that hemi-specific binding is more prevalent in p53 REs than previously envisioned. We reveal that sequences flanking the REs modulate p53 binding and activity and show that these effects extend to 4-5 bp from the REs. Moreover, we show here that the arrangement of p53 half-sites within its REs, relative to transcription direction, has been fine-tuned by selection pressure to optimize and regulate the response levels from p53 REs. This directionality in the REs arrangement is at least partly encoded in the structural properties of the REs. Furthermore, we show here that in the p21-5' RE the orientation of the half-sites is such that the effect of the flanking sequences is minimized and we discuss its advantages.
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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.