ArticlePloS one2013
WW domain containing E3 ubiquitin protein ligase 1 (WWP1) negatively regulates TLR4-mediated TNF-α and IL-6 production by proteasomal degradation of TNF receptor associated factor 6 (TRAF6).
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 30 citations in OpenAlex.
- WDR23 prevents bone loss by promoting autophagic degradation of TRAF6 in osteoclastogenesis.Bone research · 2026Article
- HECT ubiquitin ligases as regulators of inflammatory signalling.Cell death and differentiation · 2026Review
- Urbanisation Drives Microevolution in the Egyptian Fruit Bat (Evolutionary applications · 2026Article
- Combining mucosal microbiome and host multi-omics data shows prognostic potential in paediatric ulcerative colitis.Nature communications · 2025Article
- Review
- EFHD2 cooperates with E3 ubiquitin ligase Smurf1 to facilitate virus infection by promoting the degradation of TRAF6 in teleost fish.Journal of virology · 2024Article
- Regulation of MAPK Signaling Pathways by the Large HERC Ubiquitin Ligases.International journal of molecular sciences · 2023Review
- Targeting WWP1 ameliorates cardiac ischemic injury by suppressing KLF15-ubiquitination mediated myocardial inflammation.Theranostics · 2023Article
- YTHDF1 alleviates sepsis by upregulating WWP1 to induce NLRP3 ubiquitination and inhibit caspase-1-dependent pyroptosis.Cell death discovery · 2022Article
- Ubiquitin-related processes and innate immunity in C. elegans.Cellular and molecular life sciences : CMLS · 2021Review
- Negative Regulation of the Innate Immune Response through Proteasomal Degradation and Deubiquitination.Viruses · 2021Review
- The Many Roles of Ubiquitin in NF-κB Signaling.Biomedicines · 2018Review
- TRAF molecules in inflammation and inflammatory diseases.Current pharmacology reports · 2018Article
- TRIM59 regulates autophagy through modulating both the transcription and the ubiquitination of BECN1.Autophagy · 2018Article
- NLRP11 disrupts MAVS signalosome to inhibit type I interferon signaling and virus-induced apoptosis.EMBO reports · 2017Article
- Inositol polyphosphate multikinase promotes Toll-like receptor-induced inflammation by stabilizing TRAF6.Science advances · 2017Article
- TLR4-induced NF-κB and MAPK signaling regulate the IL-6 mRNA stabilizing protein Arid5a.Nucleic acids research · 2017Article
- Schizandrin A Inhibits Microglia-Mediated Neuroninflammation through Inhibiting TRAF6-NF-κB and Jak2-Stat3 Signaling Pathways.PloS one · 2016Article
- Natural small molecule FMHM inhibits lipopolysaccharide-induced inflammatory response by promoting TRAF6 degradation via K48-linked polyubiquitination.Scientific reports · 2015Article
- Functional Characterization of a WWP1/Tiul1 Tumor-derived Mutant Reveals a Paradigm of Its Constitutive Activation in Human Cancer.The Journal of biological chemistry · 2015Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundToll-like receptors (TLRs) play a pivotal role in the defense against invading pathogens by detecting pathogen-associated molecular patterns (PAMPs). TLR4 recognizes lipopolysaccharides (LPS) in the cell walls of Gram-negative bacteria, resulting in the induction and secretion of proinflammatory cytokines such as TNF-α and IL-6. The WW domain containing E3 ubiquitin protein ligase 1 (WWP1) regulates a variety of cellular biological processes. Here, we investigated whether WWP1 acts as an E3 ubiquitin ligase in TLR-mediated inflammation. METHODOLOGY/
resultsKnocking down WWP1 enhanced the TNF-α and IL-6 production induced by LPS, and over-expression of WWP1 inhibited the TNF-α and IL-6 production induced by LPS, but not by TNF-α. WWP1 also inhibited the IκB-α, NF-κB, and MAPK activation stimulated by LPS. Additionally, WWP1 could degrade TRAF6, but not IRAK1, in the proteasome pathway, and knocking down WWP1 reduced the LPS-induced K48-linked, but not K63-linked, polyubiquitination of endogenous TRAF6. CONCLUSIONS/SIGNIFICANCE: We identified WWP1 as an important negative regulator of TLR4-mediated TNF-α and IL-6 production. We also showed that WWP1 functions as an E3 ligase when cells are stimulated with LPS by binding to TRAF6 and promoting K48-linked polyubiquitination. This results in the proteasomal degradation of TRAF6.
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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.