ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
E3 Ubiquitin Ligase RNF13 Suppresses TLR Lysosomal Degradation by Promoting LAMP-1 Proteasomal Degradation.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Mechanical Unloading Inhibits Osteoblast Differentiation via Downregulation of OGT-Mediated O-GlcNAcylation.Current issues in molecular biology · 2026Article
- Tissue-Resident Macrophage in Inflammation and Cancer.MedComm · 2026Review
- RNF13 is a previously undescribed interactor of iduronate 2-sulfatase that modifies its glycosylation and maturation.The FEBS journal · 2026Article
- Targeting post-translational modifications: novel insights into bone metabolic diseases.Journal of advanced research · 2026Review
- PRKCQ-TRIM22 axis promotes proliferation and metastasis of oral squamous cell carcinoma via autophagosome‒lysosome pathway activation.Cancer cell international · 2026Article
- Exploring the Shared Diagnostic Biomarkers and Molecular Mechanisms Related to Mitochondrial Dysfunction in Inflammatory Bowel Disease and Rheumatoid Arthritis.Current issues in molecular biology · 2026Article
- Toll-like receptors in innate immunity and inflammation: from fundamental biology to clinic insights.Immunity & inflammation · 2026Review
- Exploring the ubiquitination regulatory network: opening new perspectives for rheumatoid arthritis therapy.Annals of medicine · 2025Review
- CDC26 facilitates ferroptosis through SLC7A11 degradation and cell cycle arrest.Clinical and experimental medicine · 2025Article
- RNF13 variants L311S and L312P associated with developmental epileptic encephalopathy alter dendritic organization in hippocampal neurons.IBRO neuroscience reports · 2025Article
- Noncoding RNA-encoded peptides in cancer: biological functions, posttranslational modifications and therapeutic potential.Journal of hematology & oncology · 2025Review
- Cell-free mitochondrial DNA as a pro-inflammatory agent in blood circulation: mechanisms, therapeutic implications, and clinical challenges in immune dysregulation.Frontiers in immunology · 2025Review
- The emerging roles of ubiquitin-like modifications in regulating HIV replication and host defense.Frontiers in cellular and infection microbiology · 2025Review
- TBC1D15 Inhibits Autophagy of Microglia through Maintaining the Damaged Swelling Lysosome in Alzheimer's Disease.Aging and disease · 2024Article
- E3 Ubiquitin Ligase RNF13 Suppresses TLR Lysosomal Degradation by Promoting LAMP-1 Proteasomal Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
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Authors and funding
6 authors.
Funding
Abstract
As a highly organized system, endo-lysosomes play a crucial role in maintaining immune homeostasis. However, the mechanisms involved in regulating endo-lysosome progression and subsequent inflammatory responses are not fully understood. By screening 103 E3 ubiquitin ligases in regulating endo-lysosomal acidification, it is discovered that lysosomal RNF13 inhibits lysosome maturation and promotes inflammatory responses mediated by endosomal Toll-like receptors (TLRs) in macrophages. Mechanistically, RNF13 mediates K48-linked polyubiquitination of LAMP-1 at residue K128 for proteasomal degradation. Upon TLRs activation, LAMP-1 promotes lysosomes maturation, which accelerates lysosomal degradation of TLRs and reduces TLR signaling in macrophages. Furthermore, peripheral blood mononuclear cells (PBMCs) from patients with rheumatoid arthritis (RA) show increased RNF13 levels and decreased LAMP-1 expression. Accordingly, the immunosuppressive agent hydroxychloroquine (HCQ) can increase the polyubiquitination of RNF13. Taken together, the study establishes a linkage between proteasomal and lysosomal degradation mechanisms for the induction of appropriate innate immune response, and offers a promising approach for the treatment of inflammatory diseases by targeting intracellular TLRs.
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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 Socratic graph.