ArticleProceedings of the National Academy of Sciences of the United States of America2020
14-3-3ζ-TRAF5 axis governs interleukin-17A signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Temporal transcriptomic profiling uncovers multilevel suppression of RANKL-driven osteoclast differentiation by 14-3-3ζ.The Journal of biological chemistry · 2026Article
- Dual role of IL-17A in COPD: amplifier of inflammatory cascades and mediator of airway remodeling and alveolar destruction.Frontiers in immunology · 2026Review
- 14-3-3ζ suppresses RANKL signaling by destabilizing TRAF6.The Journal of biological chemistry · 2024Article
- Article
- Sirt1 Overexpression Inhibits Fibrous Scar Formation and Improves Functional Recovery After Cerebral Ischemic Injury Through the Deacetylation of 14-3-3ζ.Molecular neurobiology · 2023Article
- A ubiquitination-mediated degradation system to target 14-3-3-binding phosphoproteins.Heliyon · 2023Article
- IRF3 inhibits nuclear translocation of NF-κB to prevent viral inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- 14-3-3ζ: A suppressor of inflammatory arthritis.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Association of methylation level and transcript level in TRAF5 gene with ankylosing spondylitis: a case-control study.Genes and immunity · 2021Article
- Structural feature of TRAFs, their related human diseases and therapeutic intervention.Archives of pharmacal research · 2021Review
- Cysteinyl-specialized proresolving mediators link resolution of infectious inflammation and tissue regeneration via TRAF3 activation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Capsaicin protects cardiomyocytes against lipopolysaccharide-induced damage via 14-3-3γ-mediated autophagy augmentation.Frontiers in pharmacology · 2021Article
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Authors and funding
10 authors.
Funding
Abstract
IL-17A is a therapeutic target in many autoimmune diseases. Most nonhematopoietic cells express IL-17A receptors and respond to extracellular IL-17A by inducing proinflammatory cytokines. The IL-17A signal transduction triggers two broad, TRAF6- and TRAF5-dependent, intracellular signaling pathways to produce representative cytokines (IL-6) and chemokines (CXCL-1), respectively. Our limited understanding of the cross-talk between these two branches has generated a crucial gap of knowledge, leading to therapeutics indiscriminately blocking IL-17A and global inhibition of its target genes. In previous work, we discovered an elevated expression of 14-3-3 proteins in inflammatory aortic disease, a rare human autoimmune disorder with increased levels of IL-17A. Here we report that 14-3-3ζ is essential for IL-17 signaling by differentially regulating the signal-induced IL-6 and CXCL-1. Using genetically manipulated human and mouse cells, and ex vivo and in vivo rat models, we uncovered a function of 14-3-3ζ. As a part of the molecular mechanism, we show that 14-3-3ζ interacts with several TRAF proteins; in particular, its interaction with TRAF5 and TRAF6 is increased in the presence of IL-17A. In contrast to TRAF6, we found TRAF5 to be an endogenous suppressor of IL-17A-induced IL-6 production, an effect countered by 14-3-3ζ. Furthermore, we observed that 14-3-3ζ interaction with TRAF proteins is required for the IL-17A-induced IL-6 levels. Together, our results show that 14-3-3ζ is an essential component of IL-17A signaling and IL-6 production, an effect that is suppressed by TRAF5. To the best of our knowledge, this report of the 14-3-3ζ-TRAF5 axis, which differentially regulates IL-17A-induced IL-6 and CXCL-1 production, is unique.
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