ArticleCell reports2021
Regulation of CYLD activity and specificity by phosphorylation and ubiquitin-binding CAP-Gly domains.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 38 citations in OpenAlex.
- Caspase-3 cleaves CYLD to restrict interferon signaling during mitochondrial apoptosis.EMBO reports · 2026Article
- Listeria promotes systemic infection by targeting the host deubiquitinase CYLD.Nature communications · 2026Article
- Systematic discovery of motif-based interactions of the auxiliary domains of USP family deubiquitinases.Nature communications · 2026Article
- Proximity labeling of thebioRxiv : the preprint server for biology · 2026Article
- Tumor immune microenvironment delineates progression trajectories of distinct nasopharyngeal carcinoma phenotypes.Cell reports. Medicine · 2025Article
- 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
- Review
- Dominant negative OTULIN-related autoinflammatory syndrome.The Journal of experimental medicine · 2024Article
- OTULIN-related conditions: Report of a new case and review of the literature using GenIA.Research square · 2024Article
- LUBAC promotes angiogenesis and lung tumorigenesis by ubiquitinating and antagonizing autophagic degradation of HIF1α.Oncogenesis · 2024Article
- In the moonlight: non-catalytic functions of ubiquitin and ubiquitin-like proteases.Frontiers in molecular biosciences · 2024Review
- MALT1 substrate cleavage: what is it good for?Frontiers in immunology · 2024Review
- Deubiquitinases in cancer.Nature reviews. Cancer · 2023Review
- Mechanisms underlying linear ubiquitination and implications in tumorigenesis and drug discovery.Cell communication and signaling : CCS · 2023Review
- CYLD in health and disease.Disease models & mechanisms · 2023Review
- The roles of long non-coding RNAs in the necroptotic signaling of colon cancer cells.Molecular biology reports · 2023Article
- The Potential of Cylindromatosis (CYLD) as a Therapeutic Target in Oxidative Stress-Associated Pathologies: A Comprehensive Evaluation.International journal of molecular sciences · 2023Review
- MALT1-dependent cleavage of CYLD promotes NF-κB signaling and growth of aggressive B-cell receptor-dependent lymphomas.Blood cancer journal · 2023Article
- Regulation of apoptosis by ubiquitination in liver cancer.American journal of cancer research · 2023Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Non-degradative ubiquitin chains and phosphorylation events govern signaling responses by innate immune receptors. The deubiquitinase CYLD in complex with SPATA2 is recruited to receptor signaling complexes by the ubiquitin ligase LUBAC and regulates Met1- and Lys63-linked polyubiquitin and receptor signaling outcomes. Here, we investigate the molecular determinants of CYLD activity. We reveal that two CAP-Gly domains in CYLD are ubiquitin-binding domains and demonstrate a requirement of CAP-Gly3 for CYLD activity and regulation of immune receptor signaling. Moreover, we identify a phosphorylation switch outside of the catalytic USP domain, which activates CYLD toward Lys63-linked polyubiquitin. The phosphorylated residue Ser568 is a novel tumor necrosis factor (TNF)-regulated phosphorylation site in CYLD and works in concert with Ser418 to enable CYLD-mediated deubiquitination and immune receptor signaling. We propose that phosphorylated CYLD, together with SPATA2 and LUBAC, functions as a ubiquitin-editing complex that balances Lys63- and Met1-linked polyubiquitin at receptor signaling complexes to promote LUBAC signaling.
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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.