ArticleCellular and molecular life sciences : CMLS2012
Regulation of Toll-like receptor signaling by NDP52-mediated selective autophagy is normally inactivated by A20.
Article in Cellular and molecular life sciences : CMLS, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 86 citations in OpenAlex.
- Autophagy and selective autophagy receptors: Key players against Alzheimer's disease.Neural regeneration research · 2026Article
- Regulation of Innate Immune Signaling by Autophagy.International journal of molecular sciences · 2026Review
- Role of autophagy in antiviral innate immunity.Cellular & molecular biology letters · 2026Review
- NDP52 and its emerging role in pathogenesis.Cell death & disease · 2025Review
- The Role of A20 in Cancer: Friend or Foe?Cells · 2025Review
- Gynostemma pentaphyllum (Thunb.) Makino Affects Autophagy and Improves Diabetic Peripheral Neuropathy Through TXNIP-Mediated PI3K/AKT/mTOR Signaling Pathway.Applied biochemistry and biotechnology · 2025Article
- REGγ is essential to maintain bone homeostasis by degrading TRAF6, preventing osteoporosis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Identification of autophagy receptors for the Crohn's disease-associated adherent-invasiveFrontiers in cellular and infection microbiology · 2024Article
- TBK1 phosphorylation activates LIR-dependent degradation of the inflammation repressor TNIP1.The Journal of cell biology · 2023Article
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- The downregulation of miR-129-5p relieves the inflammatory response in acute respiratory distress syndrome by regulating PPARγ-mediated autophagy.Annals of translational medicine · 2022Article
- Interactions of Autophagy and the Immune System in Health and Diseases.Autophagy reports · 2022Article
- Characterization of a natural variant of human NDP52 and its functional consequences on mitophagy.Cell death and differentiation · 2021Article
- Role of Herbal Teas in Regulating Cellular Homeostasis and Autophagy and Their Implications in Regulating Overall Health.Nutrients · 2021Review
- Crosstalk Between NDP52 and LUBAC in Innate Immune Responses, Cell Death, and Xenophagy.Frontiers in immunology · 2021Article
- Review
- The Role of Autophagy and Autophagy Receptor NDP52 in Microbial Infections.International journal of molecular sciences · 2020Review
- A20 inhibits osteoclastogenesis via TRAF6-dependent autophagy in human periodontal ligament cells under hypoxia.Cell proliferation · 2020Article
- Relative Contributions of the cGAS-STING and TLR3 Signaling Pathways to Attenuation of Herpes Simplex Virus 1 Replication.Journal of virology · 2020Article
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptor (TLR) signaling is linked to autophagy that facilitates elimination of intracellular pathogens. However, it is largely unknown whether autophagy controls TLR signaling. Here, we report that poly(I:C) stimulation induces selective autophagic degradation of the TLR adaptor molecule TRIF and the signaling molecule TRAF6, which is revealed by gene silencing of the ubiquitin-editing enzyme A20. This type of autophagy induced formation of autophagosomes and could be suppressed by an autophagy inhibitor and lysosomal inhibitors. However, this autophagy was not associated with canonical autophagic processes, including involvement of Beclin-1 and conversion of LC3-I to LC3-II. Through screening of TRIF-interacting 'autophagy receptors' in human cells, we identified that NDP52 mediated the selective autophagic degradation of TRIF and TRAF6 but not TRAF3. NDP52 was polyubiquitinated by TRAF6 and was involved in aggregation of TRAF6, which may result in the selective degradation. Intriguingly, only under the condition of A20 silencing, NDP52 could effectively suppress poly(I:C)-induced proinflammatory gene expression. Thus, this study clarifies a selective autophagic mechanism mediated by NDP52 that works downstream of TRIF-TRAF6. Furthermore, although A20 is known as a signaling fine-tuner to prevent excess TLR signaling, it paradoxically downregulates the fine-tuning effect of NDP52 on TLR signaling.
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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.