Evidence map›Paper›PMID 38055744›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2023

USP16 is an ISG15 cross-reactive deubiquitinase that targets pro-ISG15 and ISGylated proteins involved in metabolism.

Jin Gan, Adán Pinto-Fernández, Dennis Flierman, Jimmy J L L Akkermans, Darragh P O'Brien, Helene Greenwood, Hannah Claire Scott, Günter Fritz, Klaus-Peter Knobeloch, Jacques Neefjes and 6 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
4.3field-weighted citation impact, top 5% of its field
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

21 citing papers in PubMed, 26 citations in OpenAlex.

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  12. Review
  13. ISGylation: is our genome yearning for such a modification?Acta biochimica et biophysica Sinica · 2025
    Review
  14. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 5 institutions in 4 countries.

Jin GanDepartment of Cell and Chemical Biology, Division of Chemical Biology and Drug Discovery, Leiden University Medical Center, Leiden 2333 ZC, The Netherlands.
Adán Pinto-FernándezChinese Academy for Medical Sciences Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, United Kingdom.
Dennis FliermanDepartment of Cell and Chemical Biology, Division of Chemical Biology and Drug Discovery, Leiden University Medical Center, Leiden 2333 ZC, The Netherlands.
Jimmy J L L AkkermansDepartment of Cell and Chemical Biology and Oncode Institute, Leiden University Medical Center LUMC, Leiden 2333 ZC, The Netherlands.
Darragh P O'BrienTarget Discovery Institute, Nuffield Department of Medicine, Centre for Medicines Discovery, University of Oxford, Oxford OX3 7FZ, United Kingdom.
Helene GreenwoodTarget Discovery Institute, Nuffield Department of Medicine, Centre for Medicines Discovery, University of Oxford, Oxford OX3 7FZ, United Kingdom.
Hannah Claire ScottChinese Academy for Medical Sciences Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, United Kingdom.
Günter FritzDepartment of Cellular Microbiology, University of Hohenheim, Stuttgart 70599, Germany.
Klaus-Peter KnobelochInstitute of Neuropathology, Faculty of Medicine, Department of Molecular Genetics, University of Freiburg, Freiburg 79106, Germany.
Jacques NeefjesDepartment of Cell and Chemical Biology and Oncode Institute, Leiden University Medical Center LUMC, Leiden 2333 ZC, The Netherlands.
Hans van DamDepartment of Cell and Chemical Biology, Division of Chemical Biology and Drug Discovery, Leiden University Medical Center, Leiden 2333 ZC, The Netherlands.
Huib OvaaDepartment of Cell and Chemical Biology, Division of Chemical Biology and Drug Discovery, Leiden University Medical Center, Leiden 2333 ZC, The Netherlands.
Hidde L PloeghProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115.ORCID 0000-0002-1090-6071
Benedikt M KesslerChinese Academy for Medical Sciences Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, United Kingdom.ORCID 0000-0002-8160-2446
Paul P GeurinkDepartment of Cell and Chemical Biology, Division of Chemical Biology and Drug Discovery, Leiden University Medical Center, Leiden 2333 ZC, The Netherlands.ORCID 0000-0003-1849-1111
Aysegul SapmazDepartment of Cell and Chemical Biology, Division of Chemical Biology and Drug Discovery, Leiden University Medical Center, Leiden 2333 ZC, The Netherlands.ORCID 0000-0003-3942-7602
Leiden University Medical Center · NLUniversity of Oxford · GBBoston Children's Hospital · USUniversity of Freiburg · DEUniversity of Hohenheim · DE

Funding

Imposing order on the family of ubiquitin-conjugating (E2) enzymes through intracellular perturbation with nanobodiesDP1AI150593 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI PLOEGH, HIDDE L. · 2019 to 2023
$7.1M
Medical Research Council G0501068NIAID NIH HHS DP1 AI150593
6 · The paper itself

Abstract

Interferon-induced ubiquitin (Ub)-like modifier ISG15 covalently modifies host and viral proteins to restrict viral infections. Its function is counteracted by the canonical deISGylase USP18 or Ub-specific protease 18. Notwithstanding indications for the existence of other ISG15 cross-reactive proteases, these remain to be identified. Here, we identify deubiquitinase USP16 as an ISG15 cross-reactive protease by means of ISG15 activity-based profiling. Recombinant USP16 cleaved pro-ISG15 and ISG15 isopeptide-linked model substrates in vitro, as well as ISGylated substrates from cell lysates. Moreover, interferon-induced stimulation of ISGylation was increased by depletion of USP16. The USP16-dependent ISG15 interactome indicated that the deISGylating function of USP16 may regulate metabolic pathways. Targeted enzymes include malate dehydrogenase, cytoplasmic superoxide dismutase 1, fructose-bisphosphate aldolase A, and cytoplasmic glutamic-oxaloacetic transaminase 1. USP16 may thus contribute to the regulation of a subset of metabolism-related proteins during type-I interferon responses.

Indexed as

CytokinesInterferon Type IDeubiquitinating EnzymesEndopeptidasesPeptide HydrolasesUbiquitinsCytokinesDeubiquitinating EnzymesEndopeptidasesInterferon Type IPeptide HydrolasesUbiquitinsactivity-based probeISG15ISGylationmetabolismUSP16

Identifiers

PMID38055744
PMCPMC10722975
OpenAlexW4389372101

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.