ArticleThe EMBO journal2012
The E3 ligase HOIP specifies linear ubiquitin chain assembly through its RING-IBR-RING domain and the unique LDD extension.
Article in The EMBO journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
153 citing papers in PubMed, 213 citations in OpenAlex.
- Role of the MDM2/p53 axis in regulating cisplatin response in tumor cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Pyoderma gangrenosum caused by the molecular uncoupling of OTULIN catalytic activity and LUBAC binding.Nature immunology · 2026Article
- Soluble CD95L triggers Caspase-10-driven reactive oxygen species production in neutrophils and aggravates anti-neutrophil cytoplasmic antibody-vasculitis.Nature communications · 2026Article
- Lysine-11 ubiquitination drives type-I/III interferon induction by cGAS-STING and Toll-like receptors 3 and 4.Nature cell biology · 2026Article
- E2 variants for probing E3 ubiquitin ligase activities.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- OTULIN: a master regulator of linear ubiquitin homeostasis in immune signaling, inflammation, and disease.Frontiers in immunology · 2026Review
- E3 ubiquitin ligases in bone homeostasis: from regulatory mechanisms to skeletal diseases and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- Identification and characterization of a ubiquitin E3 RING ligase of the Chlamydia-like bacterium Simkania negevensis.PLoS pathogens · 2025Article
- Linear ubiquitination of p31Cell & bioscience · 2025Article
- The RBR E3 ubiquitin ligase HOIL-1 can ubiquitinate diverse non-protein substrates in vitro.Life science alliance · 2025Article
- Deciphering Key Regulatory Roles of Linear Ubiquitination in Cell Fate Determination and Disease.Research (Washington, D.C.) · 2025Review
- AlphaFold2 assists in providing novel mechanistic insights into the interactions among the LUBAC subunits.Acta biochimica et biophysica Sinica · 2024Article
- Systematic HOIP interactome profiling reveals critical roles of linear ubiquitination in tissue homeostasis.Nature communications · 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
- LUBAC promotes angiogenesis and lung tumorigenesis by ubiquitinating and antagonizing autophagic degradation of HIF1α.Oncogenesis · 2024Article
- Mechanisms underlying linear ubiquitination and implications in tumorigenesis and drug discovery.Cell communication and signaling : CCS · 2023Review
- Mechanistic insights into the enzymatic activity of E3 ligase HOIL-1L and its regulation by the linear ubiquitin chain binding.Science advances · 2023Article
- The mechanism of linear ubiquitination in regulating cell death and correlative diseases.Cell death & disease · 2023Review
93 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the NF-κB pathway requires the formation of Met1-linked 'linear' ubiquitin chains on NEMO, which is catalysed by the Linear Ubiquitin Chain Assembly Complex (LUBAC) E3 consisting of HOIP, HOIL-1L and Sharpin. Here, we show that both LUBAC catalytic activity and LUBAC specificity for linear ubiquitin chain formation are embedded within the RING-IBR-RING (RBR) ubiquitin ligase subunit HOIP. Linear ubiquitin chain formation by HOIP proceeds via a two-step mechanism involving both RING and HECT E3-type activities. RING1-IBR catalyses the transfer of ubiquitin from the E2 onto RING2, to transiently form a HECT-like covalent thioester intermediate. Next, the ubiquitin is transferred from HOIP onto the N-terminus of a target ubiquitin. This transfer is facilitated by a unique region in the C-terminus of HOIP that we termed 'Linear ubiquitin chain Determining Domain' (LDD), which may coordinate the acceptor ubiquitin. Consistent with this mechanism, the RING2-LDD region was found to be important for NF-κB activation in cellular assays. These data show how HOIP combines a general RBR ubiquitin ligase mechanism with unique, LDD-dependent specificity for producing linear ubiquitin chains.
Indexed as
Identifiers
What OpenQuestion holds
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.