ArticleThe Journal of biological chemistry2008
The RING domain and first zinc finger of TRAF6 coordinate signaling by interleukin-1, lipopolysaccharide, and RANKL.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 112 citations in OpenAlex.
- WDR23 prevents bone loss by promoting autophagic degradation of TRAF6 in osteoclastogenesis.Bone research · 2026Article
- The TRAF6-Akt axis is required for efficient lytic replication of KSHV.PLoS pathogens · 2026Article
- The dinitrothiophenol SN-2 reduces osteoclastogenesis and estrogen deficiency-induced bone loss by inhibiting TRAF6 auto-ubiquitination.Bone reports · 2026Article
- Review
- Moonlighting cytosolic function of ACAD9: suppression of TRAF6-mediated osteoclastogenesis and protection against osteoporosis.Cell death & disease · 2026Article
- The role of ubiquitination and deubiquitination in urological tumours.Frontiers in pharmacology · 2025Review
- Exploring the Role of Ubiquitin-Proteasome System in the Pathogenesis of Parkinson's Disease.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Structural Characterization of TRAF6 N-Terminal for Therapeutic Uses and Computational Studies on New Derivatives.Pharmaceuticals (Basel, Switzerland) · 2023Article
- FKBP51 plays an essential role in Akt ubiquitination that requires Hsp90 and PHLPP.Cell death & disease · 2023Article
- TRAF6 regulates the abundance of RIPK1 and inhibits the RIPK1/RIPK3/MLKL necroptosis signaling pathway and affects the progression of colorectal cancer.Cell death & disease · 2023Article
- The IRAK-M death domain: a tale of three surfaces.Frontiers in molecular biosciences · 2023Article
- Article
- The E3 Ubiquitin Ligase TRAF6 Interacts with the Cellular Prion Protein and Modulates Its Solubility and Recruitment to Cytoplasmic p62/SQSTM1-Positive Aggresome-Like Structures.Molecular neurobiology · 2022Article
- RANKL Impairs the TLR4 Pathway by Increasing TRAF6 and RANK Interaction in Macrophages.BioMed research international · 2022Article
- Article
- E3 ubiquitin ligases in the acute leukemic signaling pathways.Frontiers in physiology · 2022Review
- CCL3 Promotes Proliferation of Colorectal Cancer Related with TRAF6/NF-Contrast media & molecular imaging · 2022Article
- Emerging Roles of Non-proteolytic Ubiquitination in Tumorigenesis.Frontiers in cell and developmental biology · 2022Review
- ASB17 Facilitates the Burst of LPS-Induced Inflammation Through Maintaining TRAF6 Stability.Frontiers in cellular and infection microbiology · 2022Article
- The small RNA mascRNA differentially regulates TLR-induced proinflammatory and antiviral responses.JCI insight · 2021Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
TRAF6, a crucial adaptor molecule in innate and adaptive immunity, contains three distinct functional domains. The C-terminal TRAF domain facilitates oligomerization and sequence-specific interaction with receptors or other adaptor proteins. In conjunction with the dimeric E2 enzyme Ubc13-Uev1A, the N-terminal RING domain of TRAF6 functions as an E3 ubiquitin (Ub) ligase that facilitates its own site-specific ubiquitination through the generation of a Lys-63-linked poly-Ub chain. This modification does not cause its proteasomal degradation but rather serves as a scaffold to activate both the IKK and stress kinase pathways. Connecting the N-and C-terminal regions, the four internal zinc finger (ZF) motifs have yet to be functionally defined. In this study, we examined the role of the ZF domains in interleukin-1, lipopolysaccharide, and RANKL signaling by reconstitution of TRAF6-deficient cells with point mutations or deletions of these ZF motifs. Although ZF domains 2-4 are dispensable for activating IKK, p38, and JNK by interleukin-1 and lipopolysaccharide, the first ZF domain together with an intact RING domain of TRAF6 is essential for activating these pathways. Furthermore, TRAF6 autoubiquitination and its interaction with Ubc13 are dependent on ZF1 and an intact RING domain. Additionally, expression of TRAF6 lacking ZF2-4 in TRAF6-deficient monocytes rescues RANKL-mediated osteoclast differentiation and LPS-stimulated interleukin-6 production. These data provide evidence for the critical role of the Ub ligase activity of TRAF6, which is coordinated via the RING domain and ZF1 to supply the necessary elements in signaling by cytokines dependent upon TRAF6.
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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.