Evidence map›Paper›PMID 35585066›Full record

ArticleNature communications2022

Deubiquitinating enzymes and the proteasome regulate preferential sets of ubiquitin substrates.

Fredrik Trulsson, Vyacheslav Akimov, Mihaela Robu, Nila van Overbeek, David Aureliano Pérez Berrocal, Rashmi G Shah, Jürgen Cox, Girish M Shah, Blagoy Blagoev, Alfred C O Vertegaal

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
6.8field-weighted citation impact, top 2% 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

59 citing papers in PubMed, 84 citations in OpenAlex.

  1. Article
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  4. A refined protocol for the large-scale production of high-quality cerebral organoids.Journal of neural transmission (Vienna, Austria : 1996) · 2026
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  14. Computational Pipelines for Protein Ubiquitylation Analysis and Prediction.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  15. Article
  16. Article
  17. Review
  18. The Ubiquitin-Proteasome System in Brain Disorders: Pathogenic Pathways, Post-Translational Tweaks, and Therapeutic Frontiers.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025
    Review
  19. 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

10 authors at 4 institutions in 4 countries.

Fredrik Trulsson *Cell and Chemical Biology, Leiden University Medical Centre, Leiden, The Netherlands.ORCID 0000-0001-7999-4367
Vyacheslav Akimov *Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.ORCID 0000-0002-8377-1761
Mihaela RobuLaboratory for Skin Cancer Research, CHU de Québec Laval University Hospital Research Centre, Québec, QC, Canada.
Nila van OverbeekCell and Chemical Biology, Leiden University Medical Centre, Leiden, The Netherlands.ORCID 0000-0002-0431-3595
David Aureliano Pérez BerrocalCell and Chemical Biology, Leiden University Medical Centre, Leiden, The Netherlands.ORCID 0000-0003-0472-2601
Rashmi G ShahLaboratory for Skin Cancer Research, CHU de Québec Laval University Hospital Research Centre, Québec, QC, Canada.
Jürgen CoxComputational Systems Biochemistry Research Group, Max-Planck Institute of Biochemistry, Martinsried, Germany.ORCID 0000-0001-8597-205X
Girish M ShahLaboratory for Skin Cancer Research, CHU de Québec Laval University Hospital Research Centre, Québec, QC, Canada.ORCID 0000-0002-9291-1164
Blagoy BlagoevDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark. bab@bmb.sdu.dk.ORCID 0000-0002-3596-0066
Alfred C O VertegaalCell and Chemical Biology, Leiden University Medical Centre, Leiden, The Netherlands. vertegaal@lumc.nl.ORCID 0000-0002-7989-0493
Leiden University · NLUniversité Laval · CAUniversity of Southern Denmark · DKMax Planck Institute of Biochemistry · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The ubiquitin-proteasome axis has been extensively explored at a system-wide level, but the impact of deubiquitinating enzymes (DUBs) on the ubiquitinome remains largely unknown. Here, we compare the contributions of the proteasome and DUBs on the global ubiquitinome, using UbiSite technology, inhibitors and mass spectrometry. We uncover large dynamic ubiquitin signalling networks with substrates and sites preferentially regulated by DUBs or by the proteasome, highlighting the role of DUBs in degradation-independent ubiquitination. DUBs regulate substrates via at least 40,000 unique sites. Regulated networks of ubiquitin substrates are involved in autophagy, apoptosis, genome integrity, telomere integrity, cell cycle progression, mitochondrial function, vesicle transport, signal transduction, transcription, pre-mRNA splicing and many other cellular processes. Moreover, we show that ubiquitin conjugated to SUMO2/3 forms a strong proteasomal degradation signal. Interestingly, PARP1 is hyper-ubiquitinated in response to DUB inhibition, which increases its enzymatic activity. Our study uncovers key regulatory roles of DUBs and provides a resource of endogenous ubiquitination sites to aid the analysis of substrate specific ubiquitin signalling.

Indexed as

Proteasome Endopeptidase ComplexUbiquitinCell DivisionDeubiquitinating EnzymesUbiquitinationDeubiquitinating EnzymesProteasome Endopeptidase ComplexUbiquitin

Identifiers

PMID35585066
PMCPMC9117253
OpenAlexW4280580246

What OpenQuestion holds

Textmetadata
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.