ArticleLaboratory investigation; a journal of technical methods and pathology2019
TRAF6 neddylation drives inflammatory arthritis by increasing NF-κB activation.
Article in Laboratory investigation; a journal of technical methods and pathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- CHIP protects rheumatoid arthritis progression by targeting TRAF6 in arthritis animal models.Journal of orthopaedic translation · 2026Article
- NEDD8 Promotes the Progression and Inflammation of Keratoconus by Increasing the Expression of YAP1.Investigative ophthalmology & visual science · 2026Article
- Article
- Robinin protects chondrocytes injury via TLR2/TLR4/NF-κB signaling in osteoarthritis.Cell biochemistry and biophysics · 2025Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Neddylation of protein, a new strategy of protein post-translational modification for targeted treatment of central nervous system diseases.Frontiers in neuroscience · 2024Review
- [Differential expression of NEDD8 in different pathological types of chronic rhinosinusitis with nasal polyps].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2023Article
- Review
- Bi-allelic variants in NAE1 cause intellectual disability, ischiopubic hypoplasia, stress-mediated lymphopenia and neurodegeneration.American journal of human genetics · 2023Article
- Neddylation Regulation of Immune Responses.Research (Washington, D.C.) · 2023Review
- MicroRNA miR-24-3p Mediates the Negative Regulation of Lipopolysaccharide-Induced Endometrial Inflammatory Response by Targeting TNF Receptor-Associated Factor 6 (Journal of inflammation research · 2022Article
- Article
- Enzymatic Machinery of Ubiquitin and Ubiquitin-Like Modification Systems in Chondrocyte Homeostasis and Osteoarthritis.Current rheumatology reports · 2021Review
- Direct Conjugation of NEDD8 to the N-Terminus of a Model Protein Can Induce Degradation.Cells · 2021Article
- Cell type-specific transcriptomics identifies neddylation as a novel therapeutic target in multiple sclerosis.Brain : a journal of neurology · 2021Article
- Article
- Role of MicroRNAs in Protective Effects of Forsythoside A Against Lipopolysaccharide-Induced Inflammation in Bovine Endometrial Stromal Cells.Frontiers in veterinary science · 2021Article
- Long Non-Coding RNA Nuclear Paraspeckle Assembly Transcript 1 (NEAT1)Relieves Sepsis-Induced Kidney Injury and Lipopolysaccharide (LPS)-Induced Inflammation in HK-2 Cells.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Mechanism by which TRAF6 Participates in the Immune Regulation of Autoimmune Diseases and Cancer.BioMed research international · 2020Review
- MLN4924 Exerts a Neuroprotective Effect against Oxidative Stress via Sirt1 in Spinal Cord Ischemia-Reperfusion Injury.Oxidative medicine and cellular longevity · 2019Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neddylation is a process similar to ubiquitination, and is critical in various inflammatory diseases; however, its importance in the pathogenesis of inflammatory arthritis is not well understood. Here, we investigated the role of neddylation in collagen-induced arthritis (CIA) and its clinical relevance. We showed that neddylation-related genes, including NEDD8 and CULLIN-1, were significantly upregulated in inflamed arthritic synovia. Functionally, neddylation activation was crucial for synovitis of CIA, as the inhibition of neddylation by MLN4924 significantly suppressed synovial cell proliferation and inflammatory responses. Mechanistically, neddylation mediated inflammatory arthritis by regulating NF-κB activation in fibroblast-like synovial cells (FLSs). Furthermore, TNF receptor-associated factor 6 (TRAF6) neddylation at Lys124 was essential for IL-17A-induced NF-κB activation. Replacing the Lys-124 residue with Arg (K124R) resulted in significantly impaired conjugation of NEDD8 to TRAF6, as well as markedly attenuated IL-17A-induced NF-κB activity. Therefore, the pathogenic role of neddylation in CIA as well as its mechanism of action demonstrated here provides a new insight into understanding the role of post-transcriptional modifications in the arthritis inflammatory response.
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