Evidence map›Paper›PMID 33507233›Full record

ArticleThe Journal of cell biology2021

The deubiquitylase USP9X controls ribosomal stalling.

Anne Clancy, Claire Heride, Adán Pinto-Fernández, Hannah Elcocks, Andreas Kallinos, Katherine J Kayser-Bricker, Weiping Wang, Victoria Smith, Simon Davis, Shawn Fessler and 16 more

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in The Journal of cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.8field-weighted citation impact, top 14% 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

27 citing papers in PubMed, 43 citations in OpenAlex.

  1. Review
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  6. Proteostasis of immune checkpoint receptors.The Biochemical journal · 2025
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  8. Review
  9. Article
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  12. Review
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  16. Review
  17. A ubiquitin language communicates ribosomal distress.Seminars in cell & developmental biology · 2024
    Review
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors at 6 institutions in 3 countries.

Anne ClancyDepartment of Molecular Physiology and Cell Signaling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
Claire Heride *Department of Molecular Physiology and Cell Signaling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
Adán Pinto-Fernández *Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Hannah ElcocksDepartment of Molecular Physiology and Cell Signaling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
Andreas KallinosDepartment of Molecular Physiology and Cell Signaling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
Katherine J Kayser-BrickerFORMA Therapeutics, Watertown, MA.
Weiping WangFORMA Therapeutics, Watertown, MA.
Victoria SmithDepartment of Molecular Physiology and Cell Signaling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
Simon DavisTarget Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Shawn FesslerFORMA Therapeutics, Watertown, MA.
Crystal McKinnonFORMA Therapeutics, Watertown, MA.
Marie KatzFORMA Therapeutics, Watertown, MA.
Tim HammondsCancer Research UK Therapeutic Discovery Laboratories, London Bioscience Innovation Centre, London, UK.
Neil P JonesCancer Research UK Therapeutic Discovery Laboratories, London Bioscience Innovation Centre, London, UK.
Jonathan O'ConnellFORMA Therapeutics, Watertown, MA.
Bruce FollowsFORMA Therapeutics, Watertown, MA.
Steven MischkeFORMA Therapeutics, Watertown, MA.
Justin A CaravellaFORMA Therapeutics, Watertown, MA.
Stephanos IoannidisFORMA Therapeutics, Watertown, MA.
Christopher DinsmoreFORMA Therapeutics, Watertown, MA.
Sunkyu KimFORMA Therapeutics, Watertown, MA.
Axel BehrensAdult Stem Cell Laboratory, Francis Crick Institute, London, UK.
David KomanderUbiquitin Signalling Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Benedikt M KesslerTarget Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Sylvie UrbéDepartment of Molecular Physiology and Cell Signaling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
Michael J ClagueDepartment of Molecular Physiology and Cell Signaling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
Forma Therapeutics (United States) · USUniversity of Liverpool · GBUniversity of Oxford · GBCancer Research UK · GBThe Francis Crick Institute · GBThe University of Melbourne · AU

Funding

Medical Research Council MR/N013840/1
6 · The paper itself

Abstract

When a ribosome stalls during translation, it runs the risk of collision with a trailing ribosome. Such an encounter leads to the formation of a stable di-ribosome complex, which needs to be resolved by a dedicated machinery. The initial stalling and the subsequent resolution of di-ribosomal complexes requires activity of Makorin and ZNF598 ubiquitin E3 ligases, respectively, through ubiquitylation of the eS10 and uS10 subunits of the ribosome. We have developed a specific small-molecule inhibitor of the deubiquitylase USP9X. Proteomics analysis, following inhibitor treatment of HCT116 cells, confirms previous reports linking USP9X with centrosome-associated protein stability but also reveals a loss of Makorin 2 and ZNF598. We show that USP9X interacts with both these ubiquitin E3 ligases, regulating their abundance through the control of protein stability. In the absence of USP9X or following chemical inhibition of its catalytic activity, levels of Makorins and ZNF598 are diminished, and the ribosomal quality control pathway is impaired.

Indexed as

UbiquitinationAntibodiesBiocatalysisCarrier ProteinsCell Line, TumorHEK293 CellsHumansProtein StabilityReproducibility of ResultsRibonucleoproteinsRibosomesUbiquitin ThiolesteraseAntibodiesCarrier ProteinsMKRN2 protein, humanRibonucleoproteinsUbiquitin ThiolesteraseUSP9X protein, humanZNF598 protein, human

Identifiers

PMID33507233
PMCPMC7849821
OpenAlexW3122434279

What OpenQuestion holds

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LicenceCC BY
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.