ArticleeLife2021
The linear ubiquitin chain assembly complex (LUBAC) generates heterotypic ubiquitin chains.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 55 citations in OpenAlex.
- Excess Met1-linked ubiquitination leads to solid aggregate formation.The EMBO journal · 2026Article
- Manipulation of nonclassical ubiquitin signaling by pathogenic bacteria.Current opinion in microbiology · 2026Review
- Association of peripheral blood LUBAC and OTULIN expression with severity and outcome in acute ischemic stroke: a prospective cohort study.Frontiers in immunology · 2026Article
- A Stable Bioisostere of Ester-Linked Ubiquitin Chains Enables Decoding of Protein Interactors.Chembiochem : a European journal of chemical biology · 2026Article
- The Ubiquitin Script: writing protein fates in chains.Essays in biochemistry · 2025Review
- Induced necroptosis limitsInfection and immunity · 2025Article
- Proteostasis of immune checkpoint receptors.The Biochemical journal · 2025Review
- The RBR E3 ubiquitin ligase HOIL-1 can ubiquitinate diverse non-protein substrates in vitro.Life science alliance · 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
- Combinatorial ubiquitin code degrades deubiquitylation-protected substrates.Nature communications · 2025Article
- Secondary interactions in ubiquitin-binding domains achieve linkage or substrate specificity.Cell reports · 2024Article
- The emerging roles of non-canonical ubiquitination in proteostasis and beyond.The Journal of cell biology · 2024Review
- AlphaFold2 assists in providing novel mechanistic insights into the interactions among the LUBAC subunits.Acta biochimica et biophysica Sinica · 2024Article
- HOIL1 mediates MDA5 activation through ubiquitination of LGP2.bioRxiv : the preprint server for biology · 2024Article
- Myofiber-type-dependent 'boulder' or 'multitudinous pebble' formations across distinct amylopectinoses.Acta neuropathologica · 2024Article
- Catalysis of non-canonical protein ubiquitylation by the ARIH1 ubiquitin ligase.The Biochemical journal · 2023Article
- Mechanistic insights into the enzymatic activity of E3 ligase HOIL-1L and its regulation by the linear ubiquitin chain binding.Science advances · 2023Article
- Solution structure of the HOIL-1L NZF domain reveals a conformational switch regulating linear ubiquitin affinity.The Journal of biological chemistry · 2023Article
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Authors and funding
15 authors at 3 institutions in 3 countries.
Funding
Abstract
The linear ubiquitin chain assembly complex (LUBAC) is the only known ubiquitin ligase for linear/Met1-linked ubiquitin chain formation. One of the LUBAC components, heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1L), was recently shown to catalyse oxyester bond formation between ubiquitin and some substrates. However, oxyester bond formation in the context of LUBAC has not been directly observed. Here, we present the first 3D reconstruction of human LUBAC obtained by electron microscopy and report its generation of heterotypic ubiquitin chains containing linear linkages with oxyester-linked branches. We found that this event depends on HOIL-1L catalytic activity. By cross-linking mass spectrometry showing proximity between the catalytic RING-in-between-RING (RBR) domains, a coordinated ubiquitin relay mechanism between the HOIL-1-interacting protein (HOIP) and HOIL-1L ligases is suggested. In mouse embryonic fibroblasts, these heterotypic chains were induced by TNF, which is reduced in cells expressing an HOIL-1L catalytic inactive mutant. In conclusion, we demonstrate that LUBAC assembles heterotypic ubiquitin chains by the concerted action of HOIP and HOIL-1L.
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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.