ArticlePLoS pathogens2015
Crystal Structure of USP7 Ubiquitin-like Domains with an ICP0 Peptide Reveals a Novel Mechanism Used by Viral and Cellular Proteins to Target USP7.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 67 citations in OpenAlex.
- GMPS promotes cervical squamous cell carcinoma cell immune evasion through USP7-mediated deubiquitination of PDL1.Human cell · 2026Article
- Proteome-wide Ubiquitinome Profiling Reveals Substrate-specific Dynamics Within the USP7 Network.Molecular & cellular proteomics : MCP · 2026Article
- Mechanisms of USP7/MAGEL2 Complex Assembly and Its Mutational Disruption in Neurodevelopmental Diseases.bioRxiv : the preprint server for biology · 2026Article
- USP17L promotes the 2-cell-like program through deubiquitination of H2AK119ub1 and ZSCAN4.Nature communications · 2025Article
- USP7 Inhibitors Destabilize EBNA1 and Suppress Epstein-Barr Virus Tumorigenesis.Journal of medical virology · 2025Article
- Review
- Non-canonical regulation of the reactivation of an oncogenic herpesvirus by the OTUD4-USP7 deubiquitinases.PLoS pathogens · 2024Article
- USP7 substrates identified by proteomics analysis reveal the specificity of USP7.Genes & development · 2022Article
- Article
- Article
- Structural basis for the SUMO protease activity of the atypical ubiquitin-specific protease USPL1.Nature communications · 2022Article
- Structure of the multiple functional domains from coronavirus nonstructural protein 3.Emerging microbes & infections · 2021Article
- Article
- DNA Polymerase ι Interacts with Both the TRAF-like and UBL1-2 Domains of USP7.Journal of molecular biology · 2021Article
- Molecular Mechanisms of DUBs Regulation in Signaling and Disease.International journal of molecular sciences · 2021Review
- Role of Ubiquitin-Specific Peptidase 47 in Cancers and Other Diseases.Frontiers in cell and developmental biology · 2021Review
- Ubiquitin-Specific Peptidase 7: A Novel Deubiquitinase That Regulates Protein Homeostasis and Cancers.Frontiers in oncology · 2021Review
- The HSV-1 ubiquitin ligase ICP0: Modifying the cellular proteome to promote infection.Virus research · 2020Review
- Unstructured Biology of Proteins from Ubiquitin-Proteasome System: Roles in Cancer and Neurodegenerative Diseases.Biomolecules · 2020Article
- The Ubiquitin-Specific Protease Usp7, a Novel Merkel Cell Polyomavirus Large T-Antigen Interaction Partner, Modulates Viral DNA Replication.Journal of virology · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Herpes simplex virus-1 immediate-early protein ICP0 activates viral genes during early stages of infection, affects cellular levels of multiple host proteins and is crucial for effective lytic infection. Being a RING-type E3 ligase prone to auto-ubiquitination, ICP0 relies on human deubiquitinating enzyme USP7 for protection against 26S proteasomal mediated degradation. USP7 is involved in apoptosis, epigenetics, cell proliferation and is targeted by several herpesviruses. Several USP7 partners, including ICP0, GMPS, and UHRF1, interact through its C-terminal domain (CTD), which contains five ubiquitin-like (Ubl) structures. Despite the fact that USP7 has emerged as a drug target for cancer therapy, structural details of USP7 regulation and the molecular mechanism of interaction at its CTD have remained elusive. Here, we mapped the binding site between an ICP0 peptide and USP7 and determined the crystal structure of the first three Ubl domains bound to the ICP0 peptide, which showed that ICP0 binds to a loop on Ubl2. Sequences similar to the USP7-binding site in ICP0 were identified in GMPS and UHRF1 and shown to bind USP7-CTD through Ubl2. In addition, co-immunoprecipitation assays in human cells comparing binding to USP7 with and without a Ubl2 mutation, confirmed the importance of the Ubl2 binding pocket for binding ICP0, GMPS and UHRF1. Therefore we have identified a novel mechanism of USP7 recognition that is used by both viral and cellular proteins. Our structural information was used to generate a model of near full-length USP7, showing the relative position of the ICP0/GMPS/UHRF1 binding pocket and the structural basis by which it could regulate enzymatic activity.
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