ArticleNature communications2019
Kinetic analysis of multistep USP7 mechanism shows critical role for target protein in activity.
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.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- Virtual Screening-Guided Identification of Candidate USP7-Inhibitory Scaffolds Exhibiting Antiproliferative Activity.Pharmaceuticals (Basel, Switzerland) · 2026Article
- ZnF-UBP domains regulate deubiquitinase activity by relieving ubiquitin product inhibition.Nature communications · 2026Article
- Proteome-wide Ubiquitinome Profiling Reveals Substrate-specific Dynamics Within the USP7 Network.Molecular & cellular proteomics : MCP · 2026Article
- Small-molecule allosteric activator of ubiquitin-specific protease 7 (USP7).Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Functional spectrum of USP7 pathogenic variants in Hao-Fountain syndrome: Insights into the enzyme's activity, stability, and allosteric modulation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The C-terminal Tail of Ubiquitin-Specific Protease 7 Facilitates Ubiquitin Release and Ensures Efficient Catalytic Turnover.Journal of molecular biology · 2025Article
- Discovery of chromatin-based determinants of azacytidine and decitabine anti-cancer activity.bioRxiv : the preprint server for biology · 2025Article
- Activation dynamics of ubiquitin-specific protease 7.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Role of USP7 in the regulation of tolerogenic dendritic cell function in type 1 diabetes.Cellular & molecular biology letters · 2025Article
- Dynamic networks connect the USP14 active site region with the proteasome interaction surface.Protein science : a publication of the Protein Society · 2025Article
- The small CRL4Nature communications · 2024Article
- Cellular Assays for Dynamic Quantification of Deubiquitinase Activity and Inhibition.Journal of molecular biology · 2023Article
- Article
- Structural and functional characterization of USP47 reveals a hot spot for inhibitor design.Communications biology · 2023Article
- Targeting USP-7 by a Novel Fluorinated 5-Pyrazolyl-Urea Derivative.International journal of molecular sciences · 2023Article
- Backbone and ILV side-chain NMR resonance assignments of the catalytic domain of human deubiquitinating enzyme USP7.Biomolecular NMR assignments · 2022Article
- The USP7-TRIM27 axis mediates non-canonical PRC1.1 function and is a druggable target in leukemia.iScience · 2021Article
- Exploring the Versatility of the Covalent Thiol-Alkyne Reaction with Substituted Propargyl Warheads: A Deciding Role for the Cysteine Protease.Journal of the American Chemical Society · 2021Article
- Deubiquitylases in developmental ubiquitin signaling and congenital diseases.Cell death and differentiation · 2021Review
- USP7 Is a Master Regulator of Genome Stability.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
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.