ArticlePLoS pathogens2020
STUB1 is targeted by the SUMO-interacting motif of EBNA1 to maintain Epstein-Barr Virus latency.
Article in PLoS pathogens, 2020. 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, 26 citations in OpenAlex.
- Oncogenic viral infection triggers LAMP2A SUMOylation and chaperone-mediated autophagy to promote tumorigenesis.Nature microbiology · 2026Article
- Association of EBV EBNA1 C-terminal variations with severity of Invasive ductal carcinoma.Molecular biology reports · 2026Article
- EBNA1 SUMOylation by PIAS1 suppresses EBV lytic replication and enhances episome maintenance.mBio · 2026Article
- The E3 ubiquitin ligase STUB1 inhibits Senecavirus A replication by mediating VP1 ubiquitination and proteasomal degradation.Journal of virology · 2025Article
- EBNA1 SUMOylation by PIAS1 Suppresses EBV Lytic Replication and Enhances Episome Maintenance.bioRxiv : the preprint server for biology · 2025Article
- Chromatin Control of EBV Infection and Latency.Current topics in microbiology and immunology · 2025Article
- Epstein-Barr virus-infected nasopharyngeal carcinoma therapeutics: oncoprotein targets and clinical implications.Medical oncology (Northwood, London, England) · 2025Review
- SUMOylation of SARS-CoV-2 spike protein is a key target for broad-spectrum antiviral therapy.Theranostics · 2025Article
- KAP1 in antiviral immunity: dual roles in viral silencing and immune regulation.Frontiers in cellular and infection microbiology · 2025Review
- KAP1/TRIM28 - antiviral and proviral protagonist of herpesvirus biology.Trends in microbiology · 2024Article
- The Epstein-Barr Virus Nuclear Antigen 1 Variant Associated with Nasopharyngeal Carcinoma Defines the Sequence Criteria for Serologic Risk Prediction.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Virus-Host Protein Interaction Network of the Hepatitis E Virus ORF2-4 by Mammalian Two-Hybrid Assays.Viruses · 2023Article
- E3 Ubiquitin Ligases in Gammaherpesviruses and HIV: A Review of Virus Adaptation and Exploitation.Viruses · 2023Review
- Regulation of EBNA1 protein stability and DNA replication activity by PLOD1 lysine hydroxylase.PLoS pathogens · 2023Article
- EBV and Lymphomagenesis.Cancers · 2023Review
- Functional diversity: update of the posttranslational modification of Epstein-Barr virus coding proteins.Cellular and molecular life sciences : CMLS · 2022Review
- Article
- SUMOylation in Viral Replication and Antiviral Defense.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Review
- Stress-Induced Epstein-Barr Virus Reactivation.Biomolecules · 2021Review
- Proteomic approaches to investigate gammaherpesvirus biology and associated tumorigenesis.Advances in virus research · 2021Review
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Latent Epstein-Barr virus (EBV) infection is strongly associated with several malignancies, including B-cell lymphomas and epithelial tumors. EBNA1 is a key antigen expressed in all EBV-associated tumors during latency that is required for maintenance of the EBV episome DNA and the regulation of viral gene transcription. However, the mechanism utilized by EBV to maintain latent infection at the levels of posttranslational regulation remains largely unclear. Here, we report that EBNA1 contains two SUMO-interacting motifs (SIM2 and SIM3), and mutation of SIM2, but not SIM3, dramatically disrupts the EBNA1 dimerization, while SIM3 contributes to the polySUMO2 modification of EBNA1 at lysine 477 in vitro. Proteomic and immunoprecipitation analyses further reveal that the SIM3 motif is required for the EBNA1-mediated inhibitory effects on SUMO2-modified STUB1, SUMO2-mediated degradation of USP7, and SUMO1-modified KAP1. Deletion of the EBNASIM motif leads to functional loss of both EBNA1-mediated viral episome maintenance and lytic gene silencing. Importantly, hypoxic stress induces the SUMO2 modification of EBNA1, and in turn the dissociation of EBNA1 with STUB1, KAP1 and USP7 to increase the SUMO1 modification of both STUB1 and KAP1 for reactivation of lytic replication. Therefore, the EBNA1SIM motif plays an essential role in EBV latency and is a potential therapeutic target against EBV-associated cancers.
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