ArticleThe Journal of biological chemistry2012
Proteolytic processing regulates Toll-like receptor 3 stability and endosomal localization.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 89 citations in OpenAlex.
- Chlamydia trachomatis serovar D replicates in uroepithelial T24/83 cells in the absence of overt inflammation.Scientific reports · 2026Article
- Involvement of nucleic acid-sensing toll-like receptors in human diseases and their controlling mechanisms.Journal of biomedical science · 2025Review
- Cell surface RNA biology: new roles for RNA binding proteins.Trends in biochemical sciences · 2025Review
- Specific binding sites on Rhesus rotavirus capsid protein dictate the method of endocytosis inducing the murine model of biliary atresia.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- The Src-ZNRF1 axis controls TLR3 trafficking and interferon responses to limit lung barrier damage.The Journal of experimental medicine · 2023Article
- The subversion of toll-like receptor signaling by bacterial and viral proteases during the development of infectious diseases.Molecular aspects of medicine · 2022Review
- Review
- Cysteine Peptidase Cathepsin X as a Therapeutic Target for Simultaneous TLR3/4-mediated Microglia Activation.Molecular neurobiology · 2022Article
- New Insights into the Role of Cysteine Cathepsins in Neuroinflammation.Biomolecules · 2021Review
- Cathepsin H deficiency decreases hypoxia-ischemia-induced hippocampal atrophy in neonatal mice through attenuated TLR3/IFN-β signaling.Journal of neuroinflammation · 2021Article
- UNC93B1 Is Widely Expressed in the Murine CNS and Is Required for Neuroinflammation and Neuronal Injury Induced by MicroRNAFrontiers in immunology · 2021Article
- Transcriptomic Analysis and C-Terminal Epitope Tagging Reveal Differential Processing and Signaling of Endogenous TLR3 and TLR7.Frontiers in immunology · 2021Article
- Ubiquitination of TLR3 by TRIM3 signals its ESCRT-mediated trafficking to the endolysosomes for innate antiviral response.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- A genome-wide CRISPR screen identifies regulation factors of the TLR3 signalling pathway.Innate immunity · 2020Article
- RNA Signaling in Pulmonary Arterial Hypertension-A Double-Stranded Sword.International journal of molecular sciences · 2020Review
- Genetic Variants Predisposing Most Strongly to Type 1 Diabetes Diagnosed Under Age 7 Years Lie Near Candidate Genes That Function in the Immune System and in Pancreatic β-Cells.Diabetes care · 2020Article
- Cell Surface Expression of Endosomal Toll-Like Receptors-A Necessity or a Superfluous Duplication?Frontiers in immunology · 2020Review
- Cathepsins in Bacteria-Macrophage Interaction: Defenders or Victims of Circumstance?Frontiers in cellular and infection microbiology · 2020Review
- Participation of Endosomes in Toll-Like Receptor 3 Transportation Pathway in Murine Astrocytes.Frontiers in cellular neuroscience · 2020Article
- Innate immune responses through Toll-like receptor 3 require human-antigen-R-mediated Atp6v0d2 mRNA stabilization.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptors (TLRs) 3, 7, and 9 are innate immune receptors that recognize nucleic acids from pathogens in endosomes and initiate signaling transductions that lead to cytokine production. Activation of TLR9 for signaling requires proteolytic processing within the ectodomain by endosome-associated proteases. Whether TLR3 requires similar proteolytic processing to become competent for signaling remains unclear. Herein we report that human TLR3 is proteolytically processed to form two fragments in endosomes. Unc93b1 is required for processing by transporting TLR3 through the Golgi complex and to the endosomes. Proteolytic cleavage requires the eight-amino acid Loop1 within leucine-rich repeat 12 of the TLR3 ectodomain. Proteolytic cleavage is not required for TLR3 signaling in response to poly(I:C), although processing could modulate the degree of response toward viral double-stranded RNAs, especially in mouse cells. Both the full-length and cleaved fragments of TLR3 can bind poly(I:C) and are present in endosomes. However, although the full-length TLR3 has a half-life in HEK293T cells of 3 h, the cleaved fragments have half-lives in excess of 7 h. Inhibition of TLR3 cleavage by either treatment with cathepsin inhibitor or by a mutation in Loop1 decreased the abundance of TLR3 in endosomes targeted for lysosomal degradation.
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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.