ArticleProceedings of the National Academy of Sciences of the United States of America2023
A molecular mechanism for the "digital" response of p53 to stress.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed.
- Chronic unpredictable mild Stress- induced neurobehavioral and metabolic alteration: insights into molecular mechanisms and emerging therapeutic Strategies".Psychopharmacology · 2026Review
- The PURB-HOTAIR complex regulates p53-dependent promoter-specific transcriptional activation.Nature structural & molecular biology · 2025Article
- Role of Electron Spin, Chirality, and Charge Dynamics in Promoting the Persistence of Nascent Nucleic Acid-Peptide Complexes.The journal of physical chemistry. B · 2025Article
- Crosstalk between paralogs and isoforms influences p63-dependent regulatory element activity.Nucleic acids research · 2024Article
- Determinants of p53 DNA binding, gene regulation, and cell fate decisions.Cell death and differentiation · 2024Review
- Context dependent activity of p63-bound gene regulatory elements.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
The tumor suppressor protein p53 accumulates in response to cellular stress and consequently orchestrates the expression of multiple genes in a p53-level and time-dependent manner to overcome stress consequences, for which a molecular mechanism is currently unknown. Previously, we reported that DNA torsional flexibility distinguishes among p53 response elements (REs) and that transactivation at basal p53 levels is correlated with p53 REs flexibility. Here, we calculated the flexibility of ~200 p53 REs. By connecting functional outcomes of p53-target genes' activation to the calculated flexibility of their REs, we show that genes known to belong to pathways that are activated rapidly upon stress contain REs that are significantly more flexible relative to REs of genes known to be involved in pathways that are activated later in the response to stress. The global structural properties of several p53 REs belonging to different pathways were experimentally validated. Additionally, reporter-gene expression driven by flexible p53 REs occurred at lower p53 levels and with faster rates than expression from rigid REs. Furthermore, analysis of published endogenous mRNA levels of p53-target genes as a function of REs' flexibility showed that early versus late genes differ significantly in their flexibility properties of their REs and that highly flexible p53 REs enable high-activation level exclusively to early-response genes. Overall, we demonstrate that DNA flexibility of p53 REs contributes significantly to functional selectivity in the p53 system by facilitating the initial steps of p53-dependent target-genes expression, thereby contributing to survival versus death decisions in the p53 system.
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Registered trials
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