Evidence map›Paper›PMID 39578541›Full record

ArticleThe EMBO journal2025

STING induces HOIP-mediated synthesis of M1 ubiquitin chains to stimulate NF-κB signaling.

Tara D Fischer, Eric N Bunker, Peng-Peng Zhu, François Le Guerroué, Mahan Hadjian, Eunice Dominguez-Martin, Francesco Scavone, Robert Cohen, Tingting Yao, Yan Wang and 2 more

Abstract read
In one paragraph

Article in The EMBO journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. A PI(3,5)PNature communications · 2026
    Article
  7. Review
  8. Deubiquitinase OTULIN dampens RIG-I-dependent antiviral signaling by removing linear ubiquitination from TRAF6.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Cell biological insights into human STING variants.Cell structure and function · 2025
    Review
  15. Article
  16. Article
  17. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Tara D FischerBiochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. fischertad@nih.gov.ORCID http://orcid.org/0000-0002-6590-4401
Eric N BunkerBiochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-0368-9512
Peng-Peng ZhuBiochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0009-0004-4607-6999
François Le GuerrouéBiochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Mahan HadjianBiochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Eunice Dominguez-MartinBiochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-9457-1725
Francesco ScavoneDepartment of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO, USA.ORCID http://orcid.org/0000-0003-3560-7120
Robert CohenDepartment of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO, USA.ORCID http://orcid.org/0000-0001-7397-4138
Tingting YaoDepartment of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO, USA.
Yan WangMass Spectrometry, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-1187-9527
Achim WernerStem Cell Biochemistry Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-1051-8447
Richard J YouleBiochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. youler@ninds.nih.gov.ORCID http://orcid.org/0000-0001-9117-5241

Funding

Machine-Learning Aided Design of Avidity-Based Biosensors of Ubiquitin SignalingR01CA283904 · NCI · COLORADO STATE UNIVERSITY · PI Robert Cohen, Christopher Davis Snow · 2024 to 2026
$1.3M
NCI NIH HHS R01 CA283904
6 · The paper itself

Abstract

STING activation by cyclic dinucleotides induces IRF3- and NF-κB-mediated gene expression in mammals, as well as lipidation of LC3B at Golgi-related membranes. While mechanisms of the IRF3 response are well understood, the mechanisms of NF-κB activation via STING remain unclear. We report here that STING activation induces linear/M1-linked ubiquitin chain (M1-Ub) formation and recruitment of the LUBAC E3 ligase, HOIP, to LC3B-associated Golgi membranes where ubiquitin is also localized. Loss of HOIP prevents formation of M1-Ub chains and reduces STING-induced NF-κB and IRF3 signaling in human THP1 monocytes and mouse bone marrow-derived macrophages, without affecting STING activation. STING-induced LC3B lipidation is not required for M1-Ub chain formation or for immune-related gene expression, but the recently reported STING function in neutralizing Golgi pH may be involved. Thus, LUBAC synthesis of M1-linked ubiquitin chains mediates STING-induced innate immune signaling.

Indexed as

Membrane ProteinsNF-kappa BSignal TransductionUbiquitin-Protein LigasesAnimalsGolgi ApparatusHEK293 CellsHumansImmunity, InnateInterferon Regulatory Factor-3MacrophagesMiceSTING ProteinTHP-1 CellsUbiquitinUbiquitinationInterferon Regulatory Factor-3Membrane ProteinsNF-kappa BRNF31 protein, humanRnf31 protein, mouseSTING1 protein, humanSting1 protein, mouseSTING ProteinUbiquitinUbiquitin-Protein LigasesGolgiInnate ImmunityLC3BLUBACNFkB

Identifiers

PMID39578541
PMCPMC11696098

What OpenQuestion holds

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Registered trials

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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.