ArticleCell death & disease2017
p53 dynamics orchestrates with binding affinity to target genes for cell fate decision.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Recombinant Human Adenovirus-Medicina (Kaunas, Lithuania) · 2021Pooled it
- 45A ncRNA Expression Leads to Chromosomal Instability and Cytoskeletal Dynamics Impairment by Modulating GTSE1/p53/AurB Subcellular Localization.International journal of molecular sciences · 2026Article
- Decoding the Central Dogma: Quantitative Insights into Transcription and Translation Dynamics in the p53-Mediated DNA Damage Response.Journal of molecular biology · 2026Review
- TOPAS-Tissue: A Framework for the Simulation of the Biological Response to Ionizing Radiation at the Multi-Cellular Level.International journal of molecular sciences · 2024Article
- Determinants of p53 DNA binding, gene regulation, and cell fate decisions.Cell death and differentiation · 2024Review
- Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy.Cancer communications (London, England) · 2024Review
- MDM2 Inhibition in the Treatment of Glioblastoma: From Concept to Clinical Investigation.Biomedicines · 2023Review
- Modulation of transcription factor dynamics allows versatile information transmission.Scientific reports · 2023Article
- Review
- Modulation of signaling cross-talk between pJNK and pAKT generates optimal apoptotic response.PLoS computational biology · 2022Article
- MicroRNAs in doxorubicin-induced cardiotoxicity: The DNA damage response.Frontiers in pharmacology · 2022Review
- Mutagenic Consequences of Sublethal Cell Death Signaling.International journal of molecular sciences · 2021Review
- Attenuating role of withaferin A in the proliferation and migration of lung cancer cells via a p53-miR-27a/miR-10b pathway.Oncology letters · 2021Article
- Life and Death Decision-Making by p53 and Implications for Cancer Immunotherapy.Trends in cancer · 2021Review
- Dual roles of SIRT1 in the BAX switch through the P53 module: A mathematical modeling study.Computational and structural biotechnology journal · 2021Article
- Review
- How p53 Molecules Solve the Target DNA Search Problem: A Review.International journal of molecular sciences · 2020Review
- Article
- Coordination of miR-192 and miR-22 in p53-Mediated Cell Fate Decision.International journal of molecular sciences · 2019Article
- p53 as a hub in cellular redox regulation and therapeutic target in cancer.Journal of molecular cell biology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Emerging evidence support that temporal dynamics is pivotal for signaling molecules in orchestrating smart responses to diverse stimuli. p53 is such a signaling molecule that employs temporal dynamics for the selective activation of downstream target genes and ultimately for cell fate decision. Yet how this fine-tuned p53 machinery is quantitatively decoded remains largely unclear. Here we report a quantitative mechanism defining how p53 dynamics orchestrates with binding affinity to target genes for cell fate decision. Treating cells with a genotoxic drug doxorubicin at various doses and durations, we found that a mild and prolonged challenge triggered sequential p53 pulses and ultimately resulted in a terminal pulse enacting apoptosis in a comparable rate with that induced by an acute and high-dose treatment. To transactivate proapoptotic genes and thereafter executing apoptosis, p53 must exceed a certain threshold and accumulate for sufficient time at levels above it. Effective cumulative levels above the threshold, defined as E∫p53, but not the total accumulation levels of p53, precisely discriminate survival and apoptotic cells. p53 accumulation below this threshold, even with prolonging time to reach a total level comparable to that from the accumulation over the threshold, could not transactivate proapoptotic genes to which the binding affinity of p53 is lower than that of proarrest genes, and this property is independent of dynamic features. Our findings indicate that the dynamic feature per se does not directly control cell fate, but rather it orchestrates with the binding affinity to target genes to confer an appropriate time window for cell fate choice. Our study provides a quantitative mechanism unifying p53 dynamics and binding affinity to target genes, providing novel insights to understand how p53 can respond quantitatively to chemotherapeutic drugs, and guiding the design of metronomic regimens for chemotherapeutic drugs.
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Registered trials
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.