ArticleNature cell biology2020
The HOIL-1L ligase modulates immune signalling and cell death via monoubiquitination of LUBAC.
Article in Nature cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 92 citations in OpenAlex.
- Excess Met1-linked ubiquitination leads to solid aggregate formation.The EMBO journal · 2026Article
- Pyoderma gangrenosum caused by the molecular uncoupling of OTULIN catalytic activity and LUBAC binding.Nature immunology · 2026Article
- The atypical E3 ligase HOIL-1 safeguards the ribosome during cellular stress.Nature cell biology · 2026Article
- Linear ubiquitination triggers Amph-mediated T-tubule biogenesis.Science advances · 2026Article
- C-terminal Fragment Generated by HOIL-1 Cleavage Suppresses Inflammatory Responses of Myeloid Cells to Alleviate Colitis.Theranostics · 2026Article
- LUBAC modulates CBM complex functions downstream of TRAF6 in T cells.Nature communications · 2025Article
- The LUBAC subunit HOIL-1 promotes the progression of HBV-associated hepatocellular carcinoma independently of linear ubiquitination.Experimental & molecular medicine · 2025Article
- Review
- The RBR E3 ubiquitin ligase HOIL-1 can ubiquitinate diverse non-protein substrates in vitro.Life science alliance · 2025Article
- Linear Ubiquitination of Hemocyanin Mediated by LUBEL Regulates Innate Immunity inInternational journal of molecular sciences · 2025Article
- Primary disorders of polyubiquitination: Dual roles in autoinflammation and immunodeficiency.The Journal of experimental medicine · 2025Review
- Deciphering Key Regulatory Roles of Linear Ubiquitination in Cell Fate Determination and Disease.Research (Washington, D.C.) · 2025Review
- OTULIN Can Improve Spinal Cord Injury by the NF-κB and Wnt/β-Catenin Signaling Pathways.Molecular neurobiology · 2024Review
- Met1-linked ubiquitination in cell signaling regulation.Biophysics reports · 2024Article
- Physiological functions of ULK1/2.Journal of molecular biology · 2024Review
- Linear ubiquitination regulates the KSHV replication and transcription activator protein to control infection.Nature communications · 2024Article
- A de novo dominant-negative variant is associated with OTULIN-related autoinflammatory syndrome.The Journal of experimental medicine · 2024Article
- Dominant negative OTULIN-related autoinflammatory syndrome.The Journal of experimental medicine · 2024Article
- The emerging roles of non-canonical ubiquitination in proteostasis and beyond.The Journal of cell biology · 2024Review
- Biallelic human SHARPIN loss of function induces autoinflammation and immunodeficiency.Nature immunology · 2024Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The linear ubiquitin chain assembly complex (LUBAC), which consists of HOIP, SHARPIN and HOIL-1L, promotes NF-κB activation and protects against cell death by generating linear ubiquitin chains. LUBAC contains two RING-IBR-RING (RBR) ubiquitin ligases (E3), and the HOIP RBR is responsible for catalysing linear ubiquitination. We found that HOIL-1L RBR plays a crucial role in regulating LUBAC. HOIL-1L RBR conjugates monoubiquitin onto all LUBAC subunits, followed by HOIP-mediated conjugation of linear chains onto monoubiquitin, and these linear chains attenuate the functions of LUBAC. The introduction of E3-defective HOIL-1L mutants into cells augmented linear ubiquitination, which protected the cells against Salmonella infection and cured dermatitis caused by reduced LUBAC levels due to SHARPIN loss. Our results reveal a regulatory mode of E3 ligases in which the accessory E3 in LUBAC downregulates the main E3 by providing preferred substrates for autolinear ubiquitination. Thus, inhibition of HOIL-1L E3 represents a promising strategy for treating severe infections or immunodeficiency.
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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.