ArticleJournal of the Royal Society, Interface2015
Anatomy of a negative feedback loop: the case of IκBα.
Article in Journal of the Royal Society, Interface, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 33 citations in OpenAlex.
- Dysregulated NF-κB dynamics impair proteostasis and drive premature differentiation in aging B cell development.Cell press blue · 2026Article
- Casein kinase 1δ/ε inhibition suppresses CLL proliferation through cell-intrinsic and microenvironmental mechanisms.HemaSphere · 2026Article
- Effects of diet supplemented with water extracts ofFrontiers in veterinary science · 2025Article
- NF-κB: master regulator of cellular responses in health and disease.Immunity & inflammation · 2025Review
- Three modes of viral adaption by the heart.Science advances · 2024Article
- Three Modes of Viral Adaption by the Heart.bioRxiv : the preprint server for biology · 2024Article
- Processing stimulus dynamics by the NF-κB network in single cells.Experimental & molecular medicine · 2023Review
- Overexpression of IκB⍺ modulates NF-κB activation of inflammatory target gene expression.Frontiers in molecular biosciences · 2023Article
- NFκB signaling in T cell memory.Frontiers in immunology · 2023Review
- Systems approaches to investigate the role of NF-κB signaling in aging.The Biochemical journal · 2022Review
- Article
- IκBα is required for full transcriptional induction of some NFκB-regulated genes in response to TNF in MCF-7 cells.NPJ systems biology and applications · 2021Article
- Six distinct NFκB signaling codons convey discrete information to distinguish stimuli and enable appropriate macrophage responses.Immunity · 2021Article
- A Quantitative Modular Modeling Approach Reveals the Effects of Different A20 Feedback Implementations for the NF-kB Signaling Dynamics.Frontiers in physiology · 2020Article
- Stimulus-specificity in the Responses of Immune Sentinel Cells.Current opinion in systems biology · 2019Article
- Controlling Nuclear NF-κB Dynamics by β-TrCP-Insights from a Computational Model.Biomedicines · 2019Article
- Elevated pre-activation basal level of nuclear NF-κB in native macrophages accelerates LPS-induced translocation of cytosolic NF-κB into the cell nucleus.Scientific reports · 2019Article
- CRISPR/Cas9-mediated gene knockout reveals a guardian role of NF-κB/RelA in maintaining the homeostasis of human vascular cells.Protein & cell · 2018Article
- Resolving the NFκB Heterodimer Binding Paradox: Strain and Frustration Guide the Binding of Dimeric Transcription Factors.Journal of the American Chemical Society · 2017Article
- Stochastic dynamics of genetic broadcasting networks.Physical review. E · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The magnitude, duration and oscillation of cellular signalling pathway responses are often limited by negative feedback loops, defined as an 'activator-induced inhibitor' regulatory motif. Within the NFκB signalling pathway, a key negative feedback regulator is IκBα. We show here that, contrary to current understanding, NFκB-inducible expression is not sufficient for providing effective negative feedback. We then employ computational simulations of NFκB signalling to identify IκBα molecular properties that are critical for proper negative feedback control and test the resulting predictions in biochemical and single-cell live-imaging studies. We identified nuclear import and nuclear export of IκBα and the IκBα-NFκB complex, as well as the free IκBα half-life, as key determinants of post-induction repression of NFκB and the potential for subsequent reactivation. Our work emphasizes that negative feedback is an emergent systems property determined by multiple molecular and biophysical properties in addition to the required 'activator-induced inhibitor' relationship.
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.