ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Targeting F box protein Fbxo3 to control cytokine-driven inflammation.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
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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.
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
52 citing papers in PubMed, 72 citations in OpenAlex.
- High-throughput ligand diversification to discover chemical inducers of proximity.Nature chemical biology · 2026Article
- An adaptor for feedback regulation of heme biosynthesis by a mitochondrial protease.Science (New York, N.Y.) · 2026Article
- Targeting E3 Ubiquitin Ligases in Post-Traumatic Osteoarthritis: Therapeutic Opportunities and Pharmacological Perspectives.Pharmaceutics · 2026Review
- NSP7 Molecular Degrader Attenuates Coronaviral Infection Through the β-TrCP1/FBXO5 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Functional characterisation of components in two Plasmodium falciparum Cullin-RING-Ligase complexes.Scientific reports · 2025Article
- A haploinsufficiency restoration strategy corrects neurobehavioral deficits in Nf1+/- mice.The Journal of clinical investigation · 2025Article
- 1'-Acetoxychavicol Acetate Selectively Downregulates Tumor Necrosis Factor Receptor-Associated Factor 2 (TRAF2) Expression.Molecules (Basel, Switzerland) · 2025Article
- Identification of a gene controlling levels of the copper response regulator 1 transcription factor in Chlamydomonas reinhardtii.The Plant cell · 2024Article
- The Transcription Factor Tbx5-Dependent Epigenetic Modification Contributes to Neuropathic Allodynia by Activating TRPV1 Expression in the Dorsal Horn.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Ginsenoside Rg1 Alleviates Sepsis-Induced Acute Lung Injury by Reducing FBXO3 Stability in an mThe AAPS journal · 2024Article
- FBXO3 stabilizes USP4 and Twist1 to promote PI3K-mediated breast cancer metastasis.PLoS biology · 2023Article
- Elucidating the role of ubiquitination and deubiquitination in osteoarthritis progression.Frontiers in immunology · 2023Review
- Ubiquitin proteasome system in immune regulation and therapeutics.Current opinion in pharmacology · 2022Review
- E3 Ubiquitin Ligase FBXO3 Drives Neuroinflammation to Aggravate Cerebral Ischemia/Reperfusion Injury.International journal of molecular sciences · 2022Article
- Cross-Regulation of F-Box Protein FBXL2 with T-bet and TNF-α during Acute and Chronic Lung Allograft Rejection.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Review
- Research-Based Product Innovation to Address Critical Unmet Needs of Patients with Inflammatory Bowel Diseases.Inflammatory bowel diseases · 2021Article
- Targeting the Ubiquitin-Proteasome System for Cancer Therapeutics by Small-Molecule Inhibitors.Cancers · 2021Review
- Negative Regulation of the Innate Immune Response through Proteasomal Degradation and Deubiquitination.Viruses · 2021Review
- Noncanonical TGF-β signaling leads to FBXO3-mediated degradation of ΔNp63α promoting breast cancer metastasis and poor clinical prognosis.PLoS biology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Cytokine-driven inflammation underlies the pathobiology of a wide array of infectious and immune-related disorders. The TNFR-associated factor (TRAF) proteins have a vital role in innate immunity by conveying signals from cell surface receptors to elicit transcriptional activation of genes encoding proinflammatory cytokines. We discovered that a ubiquitin E3 ligase F box component, termed Fbxo3, potently stimulates cytokine secretion from human inflammatory cells by mediating the degradation of the TRAF inhibitory protein, Fbxl2. Analysis of the Fbxo3 C-terminal structure revealed that the bacterial-like ApaG molecular signature was indispensible for mediating Fbxl2 disposal and stimulating cytokine secretion. By targeting this ApaG motif, we developed a highly unique, selective genus of small-molecule Fbxo3 inhibitors that by reducing TRAF protein levels, potently inhibited cytokine release from human blood mononuclear cells. The Fbxo3 inhibitors effectively lessened the severity of viral pneumonia, septic shock, colitis, and cytokine-driven inflammation systemically in murine models. Thus, pharmacological targeting of Fbxo3 might be a promising strategy for immune-related disorders characterized by a heightened host inflammatory response.
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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.