ArticleNature structural & molecular biology2011
Bilateral inhibition of HAUSP deubiquitinase by a viral interferon regulatory factor protein.
Article in Nature structural & molecular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 82 citations in OpenAlex.
- Mechanisms of USP7/MAGEL2 Complex Assembly and Its Mutational Disruption in Neurodevelopmental Diseases.bioRxiv : the preprint server for biology · 2026Article
- Molecular analysis of the interaction between ubiquitin-specific protease 7 and large T antigen of Merkel cell polyomavirus.Journal of microbiology (Seoul, Korea) · 2026Article
- 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
- Effect of deubiquitinases in head and neck squamous cell carcinoma (Review).Oncology letters · 2025Review
- Disrupting the OTUD4-USP7 deubiquitinase complex to suppress herpesvirus replication: a novel antiviral strategy.PLoS pathogens · 2025Article
- Review
- Biologically significant interaction of human herpesvirus 8 viral interferon regulatory factor 4 with ubiquitin-specific protease 7.Journal of virology · 2024Article
- Non-canonical regulation of the reactivation of an oncogenic herpesvirus by the OTUD4-USP7 deubiquitinases.PLoS pathogens · 2024Article
- The Role of Deubiquitinating Enzyme in Head and Neck Squamous Cell Carcinoma.International journal of molecular sciences · 2022Review
- Herpesvirus-induced spermidine synthesis and eIF5A hypusination for viral episomal maintenance.Cell reports · 2022Article
- STAT and Janus kinase targeting by human herpesvirus 8 interferon regulatory factor in the suppression of type-I interferon signaling.PLoS pathogens · 2022Article
- PE_PGRS38 Interaction With HAUSP Downregulates Antimycobacterial Host DefenseFrontiers in immunology · 2022Article
- The ORF45 Protein of Kaposi Sarcoma-Associated Herpesvirus Is an Inhibitor of p53 Signaling during Viral Reactivation.Journal of virology · 2021Article
- Regulation of Cancer Metabolism by Deubiquitinating Enzymes: The Warburg Effect.International journal of molecular sciences · 2021Review
- Bimodal regulation of the PRC2 complex by USP7 underlies tumorigenesis.Nucleic acids research · 2021Article
- TRIMming Type I Interferon-Mediated Innate Immune Response in Antiviral and Antitumor Defense.Viruses · 2021Review
- Molecular Mechanisms of DUBs Regulation in Signaling and Disease.International journal of molecular sciences · 2021Review
- Ubiquitin-Specific Peptidase 7: A Novel Deubiquitinase That Regulates Protein Homeostasis and Cancers.Frontiers in oncology · 2021Review
- Tumor suppressor OTUD3 induces growth inhibition and apoptosis by directly deubiquitinating and stabilizing p53 in invasive breast carcinoma cells.BMC cancer · 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
12 authors at 7 institutions in 3 countries.
Funding
Abstract
Herpesvirus-associated ubiquitin-specific protease (HAUSP) regulates the stability of p53 and the p53-binding protein MDM2, implicating HAUSP as a therapeutic target for tuning p53-mediated antitumor activity. Here we report the structural analysis of HAUSP with Kaposi's sarcoma-associated herpesvirus viral interferon (IFN) regulatory factor 4 (vIRF4) and the discovery of two vIRF4-derived peptides, vif1 and vif2, as potent and selective HAUSP antagonists. This analysis reveals a bilateral belt-type interaction that results in inhibition of HAUSP. The vif1 peptide binds the HAUSP TRAF domain, competitively blocking substrate binding, whereas the vif2 peptide binds both the HAUSP TRAF and catalytic domains, robustly suppressing its deubiquitination activity. Peptide treatments comprehensively blocked HAUSP, leading to p53-dependent cell-cycle arrest and apoptosis in culture and to tumor regression in xenograft mouse model. Thus, the virus has developed a unique strategy to target the HAUSP-MDM2-p53 pathway, and these virus-derived short peptides represent biologically active HAUSP antagonists.
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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.