ArticleFrontiers in immunology2018
β-TrCP Restricts Lipopolysaccharide (LPS)-Induced Activation of TRAF6-IKK Pathway Upstream of IκBα Signaling.
Article in Frontiers in immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Article
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- FBXL8 Stabilizes IκBα and Negatively Regulated NF-κB Activation to Suppress Pancreatic Cancer Progression.International journal of biological sciences · 2026Article
- Neuroinflammation: Mechanisms, Dual Roles, and Therapeutic Strategies in Neurological Disorders.Current issues in molecular biology · 2025Review
- SKP1-CUL1-F-box: Key molecular targets affecting disease progression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Review
- Hyperoside Nanomicelles Alleviate Atherosclerosis by Modulating the Lipid Profile and Intestinal Flora Structure in High-Fat-Diet-Fed Apolipoprotein-E-Deficient Mice.Molecules (Basel, Switzerland) · 2023Article
- Protective effect of endothelial progenitor cell-derived exosomal microRNA-382-3p on sepsis-induced organ damage and immune suppression in mice.American journal of translational research · 2022Article
- YAP promotes the activation of NLRP3 inflammasome via blocking K27-linked polyubiquitination of NLRP3.Nature communications · 2021Article
- Manifold role of ubiquitin in Helicobacter pylori infection and gastric cancer.Cellular and molecular life sciences : CMLS · 2021Review
- A 2-Benzylmalonate Derivative as STAT3 Inhibitor Suppresses Tumor Growth in Hepatocellular Carcinoma by Upregulating β-TrCP E3 Ubiquitin Ligase.International journal of molecular sciences · 2021Article
- Schisandrol A Suppresses Catabolic Factor Expression by Blocking NF-κB Signaling in Osteoarthritis.Pharmaceuticals (Basel, Switzerland) · 2021Article
- The Hepatitis E Virus Open Reading Frame 2 Protein: Beyond Viral Capsid.Frontiers in microbiology · 2021Review
- Post-translational Modifications of IκBα: The State of the Art.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
β transducin repeat-containing protein (β-TrCP) is a Skp1-Cul1-F-box ubiquitin ligase, which plays important roles in controlling numerous signaling pathways. Notably, β-TrCP induces ubiquitination and degradation of inhibitor of NF-κB (IκBα), thus triggering activation of NF-κB signaling. Here, we unexpectedly find that β-TrCP restricts TRAF6-IKK signaling upstream of IκBα induced by lipopolysaccharide (LPS). In LPS-Toll-like receptor 4 (TLR4) pathway, protein kinase D1 (PKD1) is essential for activation of TRAF6-IKK-IκBα signaling including TRAF6 ubiquitination, IKK phosphorylation and subsequent IκBα degradation. We found that LPS promotes binding of β-TrCP to PKD1, and results in downregulation of PKD1 and recovery of IκBα protein level. Knockdown of β-TrCP blocks LPS-induced downregulation of PKD1. Supplement of enough PKD1 in cells inhibits recovery of IκBα protein levels during LPS stimulation. Furthermore, we demonstrate that β-TrCP inhibits LPS-induced TRAF6 ubiquitination and IKK phosphorylation. Taken together, our findings identify β-TrCP as an important negative regulator for upstream signaling of IκBα in LPS pathway, and therefore renew the understanding of the roles of β-TrCP in regulating TLRs inflammatory signaling.
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