ArticleCell reports2016
CYLD Limits Lys63- and Met1-Linked Ubiquitin at Receptor Complexes to Regulate Innate Immune Signaling.
Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 152 citations in OpenAlex.
- The Chromatin Accessibility Landscape of Peripheral Blood Mononuclear Cells in Patients With Systemic Lupus Erythematosus at Single-Cell Resolution.Frontiers in immunology · 2021Trial
- M1-linked ubiquitination by LUBAC regulates AMPK signalling and the response to energetic stress.Cell death and differentiation · 2026Article
- Reprogramming of the hepatic ubiquitin‑immune axis: A unifying mechanism in liver disease progression (Review).Molecular medicine reports · 2026Review
- Targeting noncanonical nuclear factor kappa B signalling in CYLD cutaneous syndrome by selective inhibition of IκB kinase alpha.The British journal of dermatology · 2026Article
- Deubiquitinase OTULIN dampens RIG-I-dependent antiviral signaling by removing linear ubiquitination from TRAF6.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Novel genotypes, phenotypes, and triggers in humans with OTULIN haploinsufficiency.Journal of human immunity · 2025Article
- The Molecular Toolbox for Linkage Type-Specific Analysis of Ubiquitin Signaling.Chembiochem : a European journal of chemical biology · 2025Review
- Primary disorders of polyubiquitination: Dual roles in autoinflammation and immunodeficiency.The Journal of experimental medicine · 2025Review
- The CYLD-PARP1 feedback loop regulates DNA damage repair and chemosensitivity in breast cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Current advances on RIPK2 and its inhibitors in pathological processes: a comprehensive review.Frontiers in molecular neuroscience · 2025Review
- TheBiochemistry · 2024Article
- Ripks and Neuroinflammation.Molecular neurobiology · 2024Review
- Cyld restrains the hyperactivation of synovial fibroblasts in inflammatory arthritis by regulating the TAK1/IKK2 signaling axis.Cell death & disease · 2024Article
- Dominant negative OTULIN-related autoinflammatory syndrome.The Journal of experimental medicine · 2024Article
- Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response.The EMBO journal · 2024Article
- LUBAC-mediated M1 Ub regulates necroptosis by segregating the cellular distribution of active MLKL.Cell death & disease · 2024Article
- OTULIN deficiency: focus on innate immune system impairment.Frontiers in immunology · 2024Review
- Mechanisms underlying linear ubiquitination and implications in tumorigenesis and drug discovery.Cell communication and signaling : CCS · 2023Review
- The therapeutic potential of targeting regulated non-apoptotic cell death.Nature reviews. Drug discovery · 2023Review
- An interaction between OTULIN and SCRIB uncovers roles for linear ubiquitination in planar cell polarity.Disease models & mechanisms · 2023Article
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Innate immune signaling relies on the deposition of non-degradative polyubiquitin at receptor-signaling complexes, but how these ubiquitin modifications are regulated by deubiquitinases remains incompletely understood. Met1-linked ubiquitin (Met1-Ub) is assembled by the linear ubiquitin assembly complex (LUBAC), and this is counteracted by the Met1-Ub-specific deubiquitinase OTULIN, which binds to the catalytic LUBAC subunit HOIP. In this study, we report that HOIP also interacts with the deubiquitinase CYLD but that CYLD does not regulate ubiquitination of LUBAC components. Instead, CYLD limits extension of Lys63-Ub and Met1-Ub conjugated to RIPK2 to restrict signaling and cytokine production. Accordingly, Met1-Ub and Lys63-Ub were individually required for productive NOD2 signaling. Our study thus suggests that LUBAC, through its associated deubiquitinases, coordinates the deposition of not only Met1-Ub but also Lys63-Ub to ensure an appropriate response to innate immune receptor activation.
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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.