ArticleProceedings of the National Academy of Sciences of the United States of America2019
The E3 ligase HOIL-1 catalyses ester bond formation between ubiquitin and components of the Myddosome in mammalian cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 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
99 citing papers in PubMed, 150 citations in OpenAlex.
- Excess Met1-linked ubiquitination leads to solid aggregate formation.The EMBO journal · 2026Article
- Tagging the Tank: Ubiquitin-mediated clearance of cellular energy reserves.Cell research · 2026Article
- Article
- Ubiquitin beyond the proteome: lipids, glycans, metabolites, nucleic acids, and an expanding molecular landscape.Biochemical Society transactions · 2026Review
- Glycogen and Glycosylation: Friends or Foes?Biomolecules · 2026Review
- Manipulation of nonclassical ubiquitin signaling by pathogenic bacteria.Current opinion in microbiology · 2026Review
- The atypical E3 ligase HOIL-1 safeguards the ribosome during cellular stress.Nature cell biology · 2026Article
- Survey of the human proteostasis network: the ubiquitin-proteasome system.bioRxiv : the preprint server for biology · 2026Article
- Specificity and recognition of the ADP-ribosyl-ubiquitin modification in the DNA damage response.PLoS biology · 2026Article
- Rab43 mitigates the inflammatory response in acute lung injury via MyD88 ubiquitination.Scientific reports · 2026Article
- E2 variants for probing E3 ubiquitin ligase activities.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- C-terminal Fragment Generated by HOIL-1 Cleavage Suppresses Inflammatory Responses of Myeloid Cells to Alleviate Colitis.Theranostics · 2026Article
- Monogenic disorders of the TNF signalling pathway.Nature reviews. Rheumatology · 2026Review
- 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
- Proteostasis of immune checkpoint receptors.The Biochemical journal · 2025Review
- Identification of RNF114 as ADPr-Ub reader through non-hydrolysable ubiquitinated ADP-ribose.Nature communications · 2025Article
- E2-Ub-R74G strategy reveals E2-specific ubiquitin conjugation profiles in live cells.Nature chemical biology · 2025Article
- Late-Stage Intermolecular O-Peptidylation Protocol Enabled by Sequential Acyl Transfer on Thiol-Incorporated Threonine Followed by Desulfurization.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- The RBR E3 ubiquitin ligase HOIL-1 can ubiquitinate diverse non-protein substrates in vitro.Life science alliance · 2025Article
39 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The linear ubiquitin assembly complex (LUBAC) comprises 3 components: HOIP, HOIL-1, and Sharpin, of which HOIP and HOIL-1 are both members of the RBR subfamily of E3 ubiquitin ligases. HOIP catalyses the formation of Met1-linked ubiquitin oligomers (also called linear ubiquitin), but the function of the E3 ligase activity of HOIL-1 is unknown. Here, we report that HOIL-1 is an atypical E3 ligase that forms oxyester bonds between the C terminus of ubiquitin and serine and threonine residues in its substrates. Exploiting the sensitivity of HOIL-1-generated oxyester bonds to cleavage by hydroxylamine, and macrophages from knock-in mice expressing the E3 ligase-inactive HOIL-1[C458S] mutant, we identify IRAK1, IRAK2, and MyD88 as physiological substrates of the HOIL-1 E3 ligase during Toll-like receptor signaling. HOIL-1 is a monoubiquitylating E3 ubiquitin ligase that initiates the de novo synthesis of polyubiquitin chains that are attached to these proteins in macrophages. HOIL-1 also catalyses its own monoubiquitylation in cells and most probably the monoubiquitylation of Sharpin, in which ubiquitin is also attached by an oxyester bond. Our study establishes that oxyester-linked ubiquitylation is used as an intracellular signaling mechanism.
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.