ArticlePLoS computational biology2020
A systematic approach to decipher crosstalk in the p53 signaling pathway using single cell dynamics.
Article in PLoS computational biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Universal differential equations for quantifying NF-κB-p53 signaling crosstalk.Bioinformatics (Oxford, England) · 2026Article
- Nanotoxicity of Porous Silica Nanoparticles: Physicochemical Properties and Mechanistic Cellular Endpoints.Nanomaterials (Basel, Switzerland) · 2025Review
- Computational modelling identifies primary mediators of crosstalk between DNA damage and oxidative stress responses.PLoS computational biology · 2025Article
- Linking signaling dynamics and cell fate decisions through single-cell imaging: evidence and challenges.Frontiers in cell and developmental biology · 2025Review
- Inertial effect of cell state velocity on the quiescence-proliferation fate decision.NPJ systems biology and applications · 2024Article
- Review
- Perspectives in Plant Abiotic Stress Signaling.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Interplay of Methodology and Conceptualization in Plant Abiotic Stress Signaling.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Resolving Crosstalk Between Signaling Pathways Using Mathematical Modeling and Time-Resolved Single Cell Data.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Model-based translation of DNA damage signaling dynamics across cell types.PLoS computational biology · 2022Article
- Insights on the NF-κB System Using Live Cell Imaging: Recent Developments and Future Perspectives.Frontiers in immunology · 2022Review
- Patient-Specific Modeling of Diffuse Large B-Cell Lymphoma.Biomedicines · 2021Article
- Progress and challenges in understanding the regulation and function of p53 dynamics.Biochemical Society transactions · 2021Review
- Mathematical Modelling of p53 Signalling during DNA Damage Response: A Survey.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transcription factors NF-κB and p53 are key regulators in the genotoxic stress response and are critical for tumor development. Although there is ample evidence for interactions between both networks, a comprehensive understanding of the crosstalk is lacking. Here, we developed a systematic approach to identify potential interactions between the pathways. We perturbed NF-κB signaling by inhibiting IKK2, a critical regulator of NF-κB activity, and monitored the altered response of p53 to genotoxic stress using single cell time lapse microscopy. Fitting subpopulation-specific computational p53 models to this time-resolved single cell data allowed to reproduce in a quantitative manner signaling dynamics and cellular heterogeneity for the unperturbed and perturbed conditions. The approach enabled us to untangle the integrated effects of IKK/ NF-κB perturbation on p53 dynamics and thereby derive potential interactions between both networks. Intriguingly, we find that a simultaneous perturbation of multiple processes is necessary to explain the observed changes in the p53 response. Specifically, we show interference with the activation and degradation of p53 as well as the degradation of Mdm2. Our results highlight the importance of the crosstalk and its potential implications in p53-dependent cellular functions.
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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.