ArticlePloS one2013
Mechanisms that enhance sustainability of p53 pulses.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed.
- Article
- A dynamic Boolean network reveals that the BMI1 and MALAT1 axis is associated with drug resistance by limiting miR-145-5p in non-small cell lung cancer.Non-coding RNA research · 2024Article
- Emerging role and therapeutic implications of p53 in intervertebral disc degeneration.Cell death discovery · 2023Review
- Misuse of the Michaelis-Menten rate law for protein interaction networks and its remedy.PLoS computational biology · 2020Review
- Coupling of cell fate selection model enhances DNA damage response and may underlie BE phenomenon.IET systems biology · 2020Article
- Integrative data modeling from lung and lymphatic cancer predicts functional roles for miR-34a and miR-16 in cell fate regulation.Scientific reports · 2020Article
- Roles of cellular heterogeneity, intrinsic and extrinsic noise in variability of p53 oscillation.Scientific reports · 2019Article
- System-based strategies for p53 recovery.IET systems biology · 2018Article
- Understanding non-linear effects from Hill-type dynamics with application to decoding of p53 signaling.Scientific reports · 2018Article
- Revealing determinants of two-phase dynamics of P53 network under gamma irradiation based on a reduced 2D relaxation oscillator model.IET systems biology · 2018Article
- Article
- A reaction-diffusion model for radiation-induced bystander effects.Journal of mathematical biology · 2017Article
- Reduction of multiscale stochastic biochemical reaction networks using exact moment derivation.PLoS computational biology · 2017Article
- Dynamics of p53: A Master Decider of Cell Fate.Genes · 2017Review
- Model-driven experimental approach reveals the complex regulatory distribution of p53 by the circadian factor Period 2.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Synchronizing stochastic circadian oscillators in single cells of Neurospora crassa.Scientific reports · 2016Article
- Protein sequestration versus Hill-type repression in circadian clock models.IET systems biology · 2016Review
- Multiscale modeling of tumor growth induced by circadian rhythm disruption in epithelial tissue.Journal of biological physics · 2016Article
- DNA Damage Response Is Involved in the Developmental Toxicity of Mebendazole in Zebrafish Retina.Frontiers in pharmacology · 2016Article
- MiR-192-Mediated Positive Feedback Loop Controls the Robustness of Stress-Induced p53 Oscillations in Breast Cancer Cells.PLoS computational biology · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tumor suppressor p53 protein shows various dynamic responses depending on the types and extent of cellular stresses. In particular, in response to DNA damage induced by γ-irradiation, cells generate a series of p53 pulses. Recent research has shown the importance of sustaining repeated p53 pulses for recovery from DNA damage. However, far too little attention has been paid to understanding how cells can sustain p53 pulses given the complexities of genetic heterogeneity and intrinsic noise. Here, we explore potential molecular mechanisms that enhance the sustainability of p53 pulses by developing a new mathematical model of the p53 regulatory system. This model can reproduce many experimental results that describe the dynamics of p53 pulses. By simulating the model both deterministically and stochastically, we found three potential mechanisms that improve the sustainability of p53 pulses: 1) the recently identified positive feedback loop between p53 and Rorα allows cells to sustain p53 pulses with high amplitude over a wide range of conditions, 2) intrinsic noise can often prevent the dampening of p53 pulses even after mutations, and 3) coupling of p53 pulses in neighboring cells via cytochrome-c significantly reduces the chance of failure in sustaining p53 pulses in the presence of heterogeneity among cells. Finally, in light of these results, we propose testable experiments that can reveal important mechanisms underlying p53 dynamics.
Indexed as
Identifiers
What OpenQuestion holds
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.