ArticleScience signaling2019
NF-κB signaling dynamics is controlled by a dose-sensing autoregulatory loop.
Article in Science signaling, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- Applications of synthetic biology in biomedicine.Molecular biomedicine · 2026Review
- Synthetic Toll-Like Receptors for Control of Innate Immunity With Far-Red Light.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Enzymatic DNA Reaction Networks for Orchestrating Stimuli-Dependent Temporal Molecular Pulse.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Optogenetic engineering of synthetic and natural receptors: design principles, functional mechanisms and biomedical applications.Regenerative biomaterials · 2026Review
- Activation of NF-κB Signaling by Optogenetic Clustering of IKKα and β.Advanced biology · 2025Article
- Decoding NF-κB: nucleocytoplasmic shuttling dynamics, synthetic modulation and post-therapeutic behavior in cancer.Molecular biology reports · 2025Review
- Transcription Factors and Methods for the Pharmacological Correction of Their Activity.International journal of molecular sciences · 2025Review
- Macrophage memory emerges from coordinated transcription factor and chromatin dynamics.Cell systems · 2025Article
- Light-dependent modulation of protein localization and function in living bacteria cells.Nature communications · 2024Article
- Article
- Co-imaging of RelA and c-Rel reveals features of NF-κB signaling for ligand discrimination.Cell reports · 2024Article
- Development of an optogenetics tool, Opto-RANK, for control of osteoclast differentiation using blue light.Scientific reports · 2024Article
- Evidence of collective influence in innate sensing using fluidic force microscopy.Frontiers in immunology · 2024Article
- Processing stimulus dynamics by the NF-κB network in single cells.Experimental & molecular medicine · 2023Review
- Myddosome clustering in IL-1 receptor signaling regulates the formation of an NF-kB activating signalosome.EMBO reports · 2023Article
- Mutations in the Vicinity of the IRAK3 Guanylate Cyclase Center Impact Its Subcellular Localization and Ability to Modulate Inflammatory Signaling in Immortalized Cell Lines.International journal of molecular sciences · 2023Article
- High-throughput co-culture system for analysis of spatiotemporal cell-cell signaling.Biosensors & bioelectronics · 2023Article
- Overexpression of IκB⍺ modulates NF-κB activation of inflammatory target gene expression.Frontiers in molecular biosciences · 2023Article
- Double knockin mice show NF-κB trajectories in immune signaling and aging.Cell reports · 2022Article
- Targeting macrophage endocytosis via platelet membrane coating for advanced osteoimmunomodulation.iScience · 2022Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Over the last decade, multiple studies have shown that signaling proteins activated in different temporal patterns, such as oscillatory, transient, and sustained, can result in distinct gene expression patterns or cell fates. However, the molecular events that ensure appropriate stimulus- and dose-dependent dynamics are not often understood and are difficult to investigate. Here, we used single-cell analysis to dissect the mechanisms underlying the stimulus- and dose-encoding patterns in the innate immune signaling network. We found that Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling dynamics relied on a dose-dependent, autoinhibitory loop that rendered cells refractory to further stimulation. Using inducible gene expression and optogenetics to perturb the network at different levels, we identified IL-1R-associated kinase 1 (IRAK1) as the dose-sensing node responsible for limiting signal flow during the innate immune response. Although the kinase activity of IRAK1 was not required for signal propagation, it played a critical role in inhibiting the nucleocytoplasmic oscillations of the transcription factor NF-κB. Thus, protein activities that may be "dispensable" from a topological perspective can nevertheless be essential in shaping the dynamic response to the external environment.
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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.