ArticleProceedings of the National Academy of Sciences of the United States of America2012
Core circadian protein CLOCK is a positive regulator of NF-κB-mediated transcription.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 199 papers.
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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.
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Who cites it
199 citing papers in PubMed, 307 citations in OpenAlex.
- Blue Light Enhances Bacterial Clearance and Reduces Organ Injury During Sepsis.Critical care medicine · 2018Trial
- BMAL1 Overexpression in the SCN Confers Protection Against Anxiety-Like Behaviors of Chronic Sleep Restricted-Mice.Molecular neurobiology · 2026Article
- Restoration of circadian rhythm as novel targets against sarcopenia.Chinese medical journal · 2026Review
- The circadian architecture of tumor immunity: mechanistic insights and treatment strategies.Biomarker research · 2026Review
- Fat body CLOCK restrains innate immunity and maintains survival under dietary stress inbioRxiv : the preprint server for biology · 2026Article
- Neuroinflammatory suppression of astrocytic BMAL1 defines a selective reactive astrocyte program.Journal of neuroinflammation · 2026Article
- Microglia depletion alleviates the disruptions in circadian rhythms and anxiety caused by bmal1 deficiency.Brain, behavior, & immunity - health · 2026Article
- Circadian Disruption Exacerbates Innate Immune Responses by Modulating the Bistability of Pro-Inflammatory Signaling: A Dynamical Modeling Study.Biomedicines · 2026Article
- The clockwork macrophage: Timing in innate immunity.Biomedical journal · 2026Review
- A temporal dialogue between the circadian clock and chronic inflammatory diseases.Disease models & mechanisms · 2026Review
- HIV disrupts the lung molecular clock, leading to lung inflammation and features of emphysema.Communications biology · 2026Article
- Comorbidity of anxiety and dry eye disease: shared biomarkers and immune responses.Frontiers in immunology · 2026Article
- Short-term continuous light exposure induces hippocampal rhythmic and functional alterations: a multi-timepoint metabolomics study.Frontiers in molecular biosciences · 2026Article
- The oral immune and inflammatory network under circadian clock control.Frontiers in immunology · 2026Review
- Autonomous Oscillations of NF-κB.Advances in experimental medicine and biology · 2026Review
- CLOCK-mediated acetylation of NF-κB p65 drives immune evasion in breast cancer.Biology direct · 2025Article
- Association ofInternational journal of molecular sciences · 2025Article
- Role of circadian CLOCK signaling in cellular senescence.Biogerontology · 2025Review
- The circadian clock, metabolism, and inflammation-the holy trinity of inflammatory bowel diseases.Clinical science (London, England : 1979) · 2025Review
- BMAL1 in Ischemic Heart Disease: A Narrative Review from Molecular Clock to Myocardial Pathology.International journal of molecular sciences · 2025Review
139 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The circadian clock controls many physiological parameters including immune response to infectious agents, which is mediated by activation of the transcription factor NF-κB. It is widely accepted that circadian regulation is based on periodic changes in gene expression that are triggered by transcriptional activity of the CLOCK/BMAL1 complex. Through the use of a mouse model system we show that daily variations in the intensity of the NF-κB response to a variety of immunomodulators are mediated by core circadian protein CLOCK, which can up-regulate NF-κB-mediated transcription in the absence of BMAL1; moreover, BMAL1 counteracts the CLOCK-dependent increase in the activation of NF-κB-responsive genes. Consistent with its regulatory function, CLOCK is found in protein complexes with the p65 subunit of NF-κB, and its overexpression correlates with an increase in specific phosphorylated and acetylated transcriptionally active forms of p65. In addition, activation of NF-κB in response to immunostimuli in mouse embryonic fibroblasts and primary hepatocytes isolated from Clock-deficient mice is significantly reduced compared with WT cells, whereas Clock-Δ19 mutation, which reduces the transactivation capacity of CLOCK on E-box-containing circadian promoters, has no effect on the ability of CLOCK to up-regulate NF-κB-responsive promoters. These findings establish a molecular link between two essential determinants of the circadian and immune mechanisms, the transcription factors CLOCK and NF-κB, respectively.
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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.