Evidence map›Paper›PMID 30651545›Full record

ArticleNature communications2019

Kinetic analysis of multistep USP7 mechanism shows critical role for target protein in activity.

Robbert Q Kim, Paul P Geurink, Monique P C Mulder, Alexander Fish, Reggy Ekkebus, Farid El Oualid, Willem J van Dijk, Duco van Dalen, Huib Ovaa, Hugo van Ingen and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. 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
1.3field-weighted citation impact, top 21% 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, 41 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Small-molecule allosteric activator of ubiquitin-specific protease 7 (USP7).Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Activation dynamics of ubiquitin-specific protease 7.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  9. Article
  10. Article
  11. The small CRL4Nature communications · 2024
    Article
  12. Article
  13. Article
  14. Article
  15. Targeting USP-7 by a Novel Fluorinated 5-Pyrazolyl-Urea Derivative.International journal of molecular sciences · 2023
    Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. USP7 Is a Master Regulator of Genome Stability.Frontiers in cell and developmental biology · 2020
    Review
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

11 authors at 4 institutions in 1 country.

Robbert Q KimDivision of Biochemistry and Oncode Institute, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands.
Paul P GeurinkDivision of Cell Biology II, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands.
Monique P C MulderDivision of Cell Biology II, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0001-5386-7132
Alexander FishDivision of Biochemistry and Oncode Institute, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands.
Reggy EkkebusDivision of Cell Biology II, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands.
Farid El OualidUbiQ Bio BV, Science Park 408, 1098 XH, Amsterdam, the Netherlands.
Willem J van DijkDivision of Biochemistry and Oncode Institute, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands.
Duco van DalenDivision of Cell Biology II, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands.
Huib OvaaDivision of Cell Biology II, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands. h.ovaa@lumc.nl.
Hugo van IngenMacromolecular Biochemistry, Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands. H.vanIngen@uu.nl.
Titia K SixmaDivision of Biochemistry and Oncode Institute, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands. t.sixma@nki.nl.
The Netherlands Cancer Institute · NLLeiden University Medical Center · NLLeiden University · NLRadboud University Nijmegen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

USP7 is a highly abundant deubiquitinating enzyme (DUB), involved in cellular processes including DNA damage response and apoptosis. USP7 has an unusual catalytic mechanism, where the low intrinsic activity of the catalytic domain (CD) increases when the C-terminal Ubl domains (Ubl45) fold onto the CD, allowing binding of the activating C-terminal tail near the catalytic site. Here we delineate how the target protein promotes the activation of USP7. Using NMR analysis and biochemistry we describe the order of activation steps, showing that ubiquitin binding is an instrumental step in USP7 activation. Using chemically synthesised p53-peptides we also demonstrate how the correct ubiquitinated substrate increases catalytic activity. We then used transient reaction kinetic modelling to define how the USP7 multistep mechanism is driven by target recognition. Our data show how this pleiotropic DUB can gain specificity for its cellular targets.

Indexed as

Protein Processing, Post-TranslationalCarbon IsotopesCatalytic DomainEnzyme AssaysKineticsModels, ChemicalMutagenesis, Site-DirectedNitrogen IsotopesNuclear Magnetic Resonance, BiomolecularPeptidesProtein BindingRecombinant ProteinsSubstrate SpecificitySurface Plasmon ResonanceTumor Suppressor Protein p53UbiquitinCarbon-13Carbon IsotopesNitrogen-15Nitrogen IsotopesPeptidesRecombinant ProteinsTP53 protein, humanTumor Suppressor Protein p53UbiquitinUbiquitin-Specific Peptidase 7USP7 protein, human

Identifiers

PMID30651545
PMCPMC6335408
OpenAlexW2909882222

What OpenQuestion holds

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LicenceCC BY
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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.