ArticleThe Journal of biological chemistry2016
Toll-like Receptor 4 Ligands Down-regulate Fcγ Receptor IIb (FcγRIIb) via MARCH3 Protein-mediated Ubiquitination.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- TLR8 Stimulation Leads to Microenvironment Activation and Enhanced Antibody-Dependent Cellular Responses in CLL.International journal of molecular sciences · 2026Article
- Review
- Differential Cell-Specific, Regulatory Roles of Fc γ Receptor IIB through IgG in IgA Nephropathy.Journal of the American Society of Nephrology : JASN · 2026Article
- Immunotherapeutic Implications of Toll-like Receptors Activation in Tumor Microenvironment.Pharmaceutics · 2022Review
- Article
- Evidence That the Etiology of Congenital Hypopituitarism Has a Major Genetic Component but Is Infrequently Monogenic.Frontiers in genetics · 2021Article
- Role of RING-Type E3 Ubiquitin Ligases in Inflammatory Signalling and Inflammatory Bowel Disease.Mediators of inflammation · 2020Review
- Characterization and functional roles of paternal RNAs in 2-4 cell bovine embryos.Scientific reports · 2019Article
- A serine in the first transmembrane domain of the human E3 ubiquitin ligase MARCH9 is critical for down-regulation of its protein substrates.The Journal of biological chemistry · 2019Article
- The Membrane-Associated MARCH E3 Ligase Family: Emerging Roles in Immune Regulation.Frontiers in immunology · 2019Review
- Soluble fibrinogen-like protein 2 ameliorates acute rejection of liver transplantation in rat via inducing Kupffer cells M2 polarization.Cancer medicine · 2018Article
- A TLR7 agonist enhances the antitumor efficacy of obinutuzumab in murine lymphoma models via NK cells and CD4 T cells.Leukemia · 2017Article
- The E3 ubiquitin ligase MARCH3 controls the endothelial barrier.FEBS letters · 2016Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Monocytes and macrophages are critical for the effectiveness of monoclonal antibody therapy. Responses to antibody-coated tumor cells are largely mediated by Fcγ receptors (FcγRs), which become activated upon binding to immune complexes. FcγRIIb is an inhibitory FcγR that negatively regulates these responses, and it is expressed on monocytes and macrophages. Therefore, deletion or down-regulation of this receptor may substantially enhance therapeutic outcomes. Here we screened a panel of Toll-like receptor (TLR) agonists and found that those selective for TLR4 and TLR8 could significantly down-regulate the expression of FcγRIIb. Upon further examination, we found that treatment of monocytes with TLR4 agonists could lead to the ubiquitination of FcγRIIb protein. A search of our earlier microarray database of monocytes activated with the TLR7/8 agonist R-848 (in which FcγRIIb was down-regulated) revealed an up-regulation of membrane-associated ring finger (C3HC4) 3 (MARCH3), an E3 ubiquitin ligase. Therefore, we tested whether LPS treatment could up-regulate MARCH3 in monocytes and whether this E3 ligase was involved with LPS-mediated FcγRIIb down-regulation. The results showed that LPS activation of TLR4 significantly increased MARCH3 expression and that siRNA against MARCH3 prevented the decrease in FcγRIIb following LPS treatment. These data suggest that activation of TLR4 on monocytes can induce a rapid down-regulation of FcγRIIb protein and that this involves ubiquitination.
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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.