ArticleProceedings of the National Academy of Sciences of the United States of America2016
Deubiquitinase CYLD acts as a negative regulator for bacterium NTHi-induced inflammation by suppressing K63-linked ubiquitination of MyD88.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 40 citations in OpenAlex.
- Proximity labeling of thebioRxiv : the preprint server for biology · 2026Article
- Rab43 mitigates the inflammatory response in acute lung injury via MyD88 ubiquitination.Scientific reports · 2026Article
- Article
- Human breast milk-derived exosomes attenuate lipopolysaccharide-induced activation in microglia.Journal of neuroinflammation · 2025Article
- Tolerance to Haemophilus influenzae infection in human epithelial cells: Insights from a primary cell-based model.PLoS pathogens · 2024Article
- OTUD5 promotes the inflammatory immune response by enhancing MyD88 oligomerization and Myddosome formation.Cell death and differentiation · 2024Article
- Regulation of ubiquitination in sepsis: from PAMP versus DAMP to peripheral inflammation and cell death.Frontiers in immunology · 2024Review
- USP3 plays a critical role in the induction of innate immune tolerance.EMBO reports · 2023Article
- CYLD in health and disease.Disease models & mechanisms · 2023Review
- The subversion of toll-like receptor signaling by bacterial and viral proteases during the development of infectious diseases.Molecular aspects of medicine · 2022Review
- Ubiquitin-specific proteases in inflammatory bowel disease-related signalling pathway regulation.Cell death & disease · 2022Review
- Integrative Proteomic Analysis of Multiple Posttranslational Modifications in Inflammatory Response.Genomics, proteomics & bioinformatics · 2022Article
- USP7 Promotes deubiquitination and stabilization of MyD88 to enhance immune responses.Frontiers in immunology · 2022Article
- Viruses utilize ubiquitination systems to escape TLR/RLR-mediated innate immunity.Frontiers in immunology · 2022Review
- Negative Regulation of the Innate Immune Response through Proteasomal Degradation and Deubiquitination.Viruses · 2021Review
- MYD88 L265P elicits mutation-specific ubiquitination to drive NF-κB activation and lymphomagenesis.Blood · 2021Article
- Toll-like receptors in sepsis-associated cytokine storm and their endogenous negative regulators as future immunomodulatory targets.International immunopharmacology · 2020Review
- Importance of Deubiquitination in Macrophage-Mediated Viral Response and Inflammation.International journal of molecular sciences · 2020Review
- Article
- SPOP promotes ubiquitination and degradation of MyD88 to suppress the innate immune response.PLoS pathogens · 2020Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Myeloid differentiation factor 88 (MyD88) acts as a crucial adaptor molecule for Toll-like receptors (TLRs) and interleukin (IL)-1 receptor signaling. In contrast to the well-studied positive regulation of MyD88 signaling, how MyD88 signaling is negatively regulated still remains largely unknown. Here, we demonstrate for the first time to our knowledge that MyD88 protein undergoes lysine 63 (K63)-linked polyubiquitination, which is functionally critical for mediating TLR-MyD88-dependent signaling. Deubiquitinase CYLD negatively regulates MyD88-mediated signaling by directly interacting with MyD88 and deubiquitinating nontypeable Haemophilus influenzae (NTHi)-induced K63-linked polyubiquitination of MyD88 at lysine 231. Importantly, we further confirmed this finding in the lungs of mice in vivo by using MyD88(-/-)CYLD(-/-) mice. Understanding how CYLD deubiquitinates K63-linked polyubiquitination of MyD88 may not only bring insights into the negative regulation of TLR-MyD88-dependent signaling, but may also lead to the development of a previously unidentified therapeutic strategy for uncontrolled inflammation.
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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 OpenQuestion graph.