ArticlePLoS computational biology2013
Dual delayed feedback provides sensitivity and robustness to the NF-κB signaling module.
Article in PLoS computational biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Review
- Analogue information processing in NF-κB gene regulatory system.Royal Society open science · 2025Article
- Stochastic switching of delayed feedback suppresses oscillations in genetic regulatory systems.Journal of the Royal Society, Interface · 2023Article
- Stochastic models of nucleosome dynamics reveal regulatory rules of stimulus-induced epigenome remodeling.Cell reports · 2022Article
- Article
- Balancing sensitivity, risk, and immunopathology in immune regulation.Current opinion in insect science · 2022Review
- Systems approaches to investigate the role of NF-κB signaling in aging.The Biochemical journal · 2022Review
- Review
- Article
- Six distinct NFκB signaling codons convey discrete information to distinguish stimuli and enable appropriate macrophage responses.Immunity · 2021Article
- Combinatorial dynamics of protein synthesis time delay and negative feedback loop in NF-IET systems biology · 2020Article
- What Will B Will B: Identifying Molecular Determinants of Diverse B-Cell Fate Decisions Through Systems Biology.Frontiers in cell and developmental biology · 2020Review
- A Quantitative Modular Modeling Approach Reveals the Effects of Different A20 Feedback Implementations for the NF-kB Signaling Dynamics.Frontiers in physiology · 2020Article
- Controlling Nuclear NF-κB Dynamics by β-TrCP-Insights from a Computational Model.Biomedicines · 2019Article
- A Noisy Analog-to-Digital Converter Connects Cytosolic Calcium Bursts to Transcription Factor Nuclear Localization Pulses in Yeast.G3 (Bethesda, Md.) · 2019Article
- Paeonol-mediated apoptosis of hepatocellular carcinoma cells by NF-κB pathway.Oncology letters · 2019Article
- An NFκB Activity Calculator to Delineate Signaling Crosstalk: Type I and II Interferons Enhance NFκB via Distinct Mechanisms.Frontiers in immunology · 2019Article
- Innate immune memory and homeostasis may be conferred through crosstalk between the TLR3 and TLR7 pathways.Science signaling · 2016Article
- Signaling via the NFκB system.Wiley interdisciplinary reviews. Systems biology and medicine · 2016Review
- Ancient trans-Acting siRNAs Confer Robustness and Sensitivity onto the Auxin Response.Developmental cell · 2016Article
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Authors and funding
6 authors.
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Abstract
Many cellular stress-responsive signaling systems exhibit highly dynamic behavior with oscillatory features mediated by delayed negative feedback loops. What remains unclear is whether oscillatory behavior is the basis for a signaling code based on frequency modulation (FM) or whether the negative feedback control modules have evolved to fulfill other functional requirements. Here, we use experimentally calibrated computational models to interrogate the negative feedback loops that regulate the dynamic activity of the transcription factor NF-κB. Linear stability analysis of the model shows that oscillatory frequency is a hard-wired feature of the primary negative feedback loop and not a function of the stimulus, thus arguing against an FM signaling code. Instead, our modeling studies suggest that the two feedback loops may be tuned to provide for rapid activation and inactivation capabilities for transient input signals of a wide range of durations; by minimizing late phase oscillations response durations may be fine-tuned in a graded rather than quantized manner. Further, in the presence of molecular noise the dual delayed negative feedback system minimizes stochastic excursions of the output to produce a robust NF-κB response.
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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.