ArticleNature chemical biology2013
Conformational stabilization of ubiquitin yields potent and selective inhibitors of USP7.
Article in Nature chemical biology, 2013. 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 57 papers.
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Who cites it
57 citing papers in PubMed, 107 citations in OpenAlex.
- Ubiquitin C-Terminal Hydrolase L1 (UCHL1), Beyond Hydrolysis.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Structure-Based Experimental Datasets for Benchmarking Protein Simulation Force Fields [Article v1.0].Living journal of computational molecular science · 2025Article
- Ubiquitin's Conformational Heterogeneity as Discerned by Nuclear Magnetic Resonance Spectroscopy.Chembiochem : a European journal of chemical biology · 2024Review
- Review
- What Strengthens Protein-Protein Interactions: Analysis and Applications of Residue Correlation Networks.Journal of molecular biology · 2023Article
- Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Structural and functional characterization of USP47 reveals a hot spot for inhibitor design.Communications biology · 2023Article
- USP7 Inhibition Suppresses Neuroblastoma Growth via Induction of p53-Mediated Apoptosis and EZH2 and N-Myc Downregulation.International journal of molecular sciences · 2023Article
- Ubiquitin Engineering for Interrogating the Ubiquitin-Proteasome System and Novel Therapeutic Strategies.Cells · 2023Review
- On the Study of Deubiquitinases: Using the Right Tools for the Job.Biomolecules · 2022Review
- Rational Development and Characterization of a Ubiquitin Variant with Selectivity for Ubiquitin C-Terminal Hydrolase L3.Biomolecules · 2022Article
- Article
- Pharmacological inhibition of USP7 suppresses growth and metastasis of melanoma cells in vitro and in vivo.Journal of cellular and molecular medicine · 2021Article
- USP7 inhibition induces apoptosis in glioblastoma by enhancing ubiquitination of ARF4.Cancer cell international · 2021Article
- Targeting the Ubiquitin-Proteasome System for Cancer Therapeutics by Small-Molecule Inhibitors.Cancers · 2021Review
- Targeting the Ubiquitin Signaling Cascade in Tumor Microenvironment for Cancer Therapy.International journal of molecular sciences · 2021Review
- Ubiquitin-Specific Peptidase 7: A Novel Deubiquitinase That Regulates Protein Homeostasis and Cancers.Frontiers in oncology · 2021Review
- Protein Engineering in the Ubiquitin System: Tools for Discovery and Beyond.Pharmacological reviews · 2020Review
- UCHL3 promotes ovarian cancer progression by stabilizing TRAF2 to activate the NF-κB pathway.Oncogene · 2020Article
- Development of a DUB-selective fluorogenic substrate.Chemical science · 2019Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein conformation and function are often inextricably linked, such that the states a protein adopts define its enzymatic activity or its affinity for various partners. Here we combine computational design with macromolecular display to isolate functional conformations of ubiquitin that tightly bind the catalytic core of the oncogenic ubiquitin-specific protease 7 (USP7) deubiquitinase. Structural and biochemical characterization of these ubiquitin variants suggest that remodeled backbone conformations and core packing poise these molecules for stronger interactions, leading to potent and specific inhibition of enzymatic activity. A ubiquitin variant expressed in human tumor cell lines binds and inhibits endogenous USP7, thereby enhancing Mdm2 proteasomal turnover and stabilizing p53. In sum, we have developed an approach to rationally target macromolecular libraries toward the remodeling of protein conformation, shown that engineering of ubiquitin conformation can greatly increase its interaction with deubiquitinases and developed powerful tools to probe the cellular role of USP7.
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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.