ArticleBMC bioinformatics2007
Single TNFalpha trimers mediating NF-kappaB activation: stochastic robustness of NF-kappaB signaling.
Article in BMC bioinformatics, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 64 citations in OpenAlex.
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- Petri nets and ODEs as complementary methods for comprehensive analysis on an example of the ATM-p53-NF-[Formula: see text]B signaling pathways.Scientific reports · 2022Article
- A variable-gain stochastic pooling motif mediates information transfer from receptor assemblies into NF-κB.Science advances · 2021Article
- A Quantitative Modular Modeling Approach Reveals the Effects of Different A20 Feedback Implementations for the NF-kB Signaling Dynamics.Frontiers in physiology · 2020Article
- Quantitative analysis reveals crosstalk mechanisms of heat shock-induced attenuation of NF-κB signaling at the single cell level.PLoS computational biology · 2018Article
- NF-κB Dynamics Discriminate between TNF Doses in Single Cells.Cell systems · 2017Article
- Information processing in the NF-κB pathway.Scientific reports · 2017Article
- Importins promote high-frequency NF-κB oscillations increasing information channel capacity.Biology direct · 2016Article
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- Clustering reveals limits of parameter identifiability in multi-parameter models of biochemical dynamics.BMC systems biology · 2015Article
- Distinct single-cell signaling characteristics are conferred by the MyD88 and TRIF pathways during TLR4 activation.Science signaling · 2015Article
- Regulation of signal transduction by spatial parameters: a case in NF-κB oscillation.IET systems biology · 2015Article
- A Kinetic-Model-Based Approach to Identify Malfunctioning Components in Signal Transduction Pathways from Artificial Clinical Data.BioMed research international · 2015Article
- The pharmacodynamics of the p53-Mdm2 targeting drug Nutlin: the role of gene-switching noise.PLoS computational biology · 2014Article
- Potential new therapeutic modality revealed through agent-based modeling of the neuromuscular junction and acetylcholinesterase inhibition.Theoretical biology & medical modelling · 2014Article
- Modeling dynamics of cell-to-cell variability in TRAIL-induced apoptosis explains fractional killing and predicts reversible resistance.PLoS computational biology · 2014Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe NF-kappaB regulatory network controls innate immune response by transducing variety of pathogen-derived and cytokine stimuli into well defined single-cell gene regulatory events.
resultsWe analyze the network by means of the model combining a deterministic description for molecular species with large cellular concentrations with two classes of stochastic switches: cell-surface receptor activation by TNFalpha ligand, and IkappaBalpha and A20 genes activation by NF-kappaB molecules. Both stochastic switches are associated with amplification pathways capable of translating single molecular events into tens of thousands of synthesized or degraded proteins. Here, we show that at a low TNFalpha dose only a fraction of cells are activated, but in these activated cells the amplification mechanisms assure that the amplitude of NF-kappaB nuclear translocation remains above a threshold. Similarly, the lower nuclear NF-kappaB concentration only reduces the probability of gene activation, but does not reduce gene expression of those responding.
conclusionThese two effects provide a particular stochastic robustness in cell regulation, allowing cells to respond differently to the same stimuli, but causing their individual responses to be unequivocal. Both effects are likely to be crucial in the early immune response: Diversity in cell responses causes that the tissue defense is harder to overcome by relatively simple programs coded in viruses and other pathogens. The more focused single-cell responses help cells to choose their individual fates such as apoptosis or proliferation. The model supports the hypothesis that binding of single TNFalpha ligands is sufficient to induce massive NF-kappaB translocation and activation of NF-kappaB dependent genes.
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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.