Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like receptors
Abstract
Activation of Toll-like receptors (TLRs) results in a proinflammatory response needed to combat infection. Thus, limiting TLR signaling is essential for preventing a protective response from causing injury to the host. Here we describe how a RING finger protein, Triad3A, acts as an E3 ubiquitin-protein ligase and enhances ubiquitination and proteolytic degradation of some TLRs. Triad3A overexpression promoted substantial degradation of TLR4 and TLR9 with a concomitant decrease in signaling, but did not affect TLR2 expression or signaling. Conversely, a reduction in endogenous Triad3A by small interfering RNA increased TLR expression and enhanced TLR activation. Thus, ubiquitination by Triad3A represents one pathway by which the intensity and duration of TLR signaling is controlled.
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Triad3A binds the cytoplasmic domain of TLR4 and TLR9 and promotes their ubiquitylation and degradation.
“Triad3A can bind to the cytoplasmic domain of TLR4 and TLR9 and promote their ubiquitylation and degradation [126]”
From Transition from inflammation to proliferation: a critical step during wound healing (2016) · cites this paper as [126]
Cites
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“, Triad3A can bind to the cytoplasmic domain of TLR4 and TLR9 and promote their ubiquitylation and degradation [126]; (d) inhibition of TLR”
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- Authors
- Chuang, T.-H., & Ulevitch, R. J.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Ulevitch, Richard J
- Venue
- Nature Immunology
- Published
- 2004-04-25
- Volume
- 5
- Issue
- 5
- Pages
- 495-502
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2040211909
- Cited by
- 374
- References
- 1
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 8 · 2023: 7 · 2022: 15 · 2021: 17 · 2020: 18 · 2019: 15 · 2018: 9 · 2017: 12 · 2016: 20 · 2015: 8 · 2014: 15 · 2013: 16 · 2012: 22
- FWCI
- 11.32
- Type
- journal article
- Language
- en
- Update notices
- erratum (2004-09-01)
- Open access
- closed
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM28485)
- National Institute of Allergy and Infectious Diseases (U54AI054523, AI 54523, AI 15136, R01AI015136)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- E3 ubiquitin ligase, RING finger protein, Toll-like receptors, TLR4, TLR9, TLR2, ubiquitination, proteolysis, innate immunity, inflammation
- MeSH terms
- Amino Acid Sequence, Carrier Proteins, Humans, Membrane Glycoproteins, Molecular Sequence Data, Receptors, Cell Surface, Ubiquitin-Protein Ligases, Intracellular Signaling Peptides and Proteins, Toll-Like Receptors, Toll-Like Receptor 2, Toll-Like Receptor 4, Toll-Like Receptor 9
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