ArticlePLoS pathogens2015
Phosphoproteomic Profiling Reveals Epstein-Barr Virus Protein Kinase Integration of DNA Damage Response and Mitotic Signaling.
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 46 papers.
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Who cites it
46 citing papers in PubMed, 67 citations in OpenAlex.
- Proteomic screening identifies HNRNPA2B1 as an epigenetic repressor of Epstein-Barr virus reactivation.Journal of virology · 2026Article
- Omics-Level Approaches to Studying Gammaherpesvirus Infection.Pathogens (Basel, Switzerland) · 2026Review
- A System-Level Perspective on Epstein-Barr Virus Persistence: The Partial Lytic Reactivation.International journal of molecular sciences · 2026Review
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- Proteomic Screening Identifies HNRNPA2B1 as an Epigenetic Repressor of Epstein-Barr Virus Reactivation.bioRxiv : the preprint server for biology · 2026Article
- Single-cell profiling of HDAC inhibitor-induced EBV lytic heterogeneity defines abortive and refractory states in B lymphoblasts.PLoS pathogens · 2026Article
- EBNA1 SUMOylation by PIAS1 suppresses EBV lytic replication and enhances episome maintenance.mBio · 2026Article
- Mechanistic Characterization of a Small Molecule as a Direct NLRP3 Inhibitor via Binding to the NACHT Domain.Journal of medicinal chemistry · 2025Article
- Single-Cell Profiling of HDAC Inhibitor-Induced EBV Lytic Heterogeneity Defines Abortive and Refractory States in B Lymphoblasts.bioRxiv : the preprint server for biology · 2025Article
- EBNA1 SUMOylation by PIAS1 Suppresses EBV Lytic Replication and Enhances Episome Maintenance.bioRxiv : the preprint server for biology · 2025Article
- RNA helicases, DDX5 and DDX17, facilitate lytic reactivation of gammaherpesviruses.PLoS pathogens · 2025Article
- Neurotropic Viruses as Acute and Insidious Drivers of Aging.Biomolecules · 2025Review
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- SUMOylation of the m6A reader YTHDF2 by PIAS1 promotes viral RNA decay to restrict EBV replication.mBio · 2024Article
- Phosphoproteomic landscape of pseudorabies virus infection reveals multiple potential antiviral targets.Microbiology spectrum · 2024Article
- Aurora Kinase A: Integrating Insights into Cancer, Inflammation, and Infectious Diseases.Gut microbes reports · 2024Review
- The alphaherpesvirus conserved pUS10 is important for natural infection and its expression is regulated by the conserved Herpesviridae protein kinase (CHPK).PLoS pathogens · 2023Article
- The ConservedViruses · 2022Article
- Caspases Switch off the mmBio · 2021Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Epstein-Barr virus (EBV) is etiologically linked to infectious mononucleosis and several human cancers. EBV encodes a conserved protein kinase BGLF4 that plays a key role in the viral life cycle. To provide new insight into the host proteins regulated by BGLF4, we utilized stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomics to compare site-specific phosphorylation in BGLF4-expressing Akata B cells. Our analysis revealed BGLF4-mediated hyperphosphorylation of 3,046 unique sites corresponding to 1,328 proteins. Frequency analysis of these phosphosites revealed a proline-rich motif signature downstream of BGLF4, indicating a broader substrate recognition for BGLF4 than its cellular ortholog cyclin-dependent kinase 1 (CDK1). Further, motif analysis of the hyperphosphorylated sites revealed enrichment in ATM, ATR and Aurora kinase substrates while functional analyses revealed significant enrichment of pathways related to the DNA damage response (DDR), mitosis and cell cycle. Phosphorylation of proteins associated with the mitotic spindle assembly checkpoint (SAC) indicated checkpoint activation, an event that inactivates the anaphase promoting complex/cyclosome, APC/C. Furthermore, we demonstrated that BGLF4 binds to and directly phosphorylates the key cellular proteins PP1, MPS1 and CDC20 that lie upstream of SAC activation and APC/C inhibition. Consistent with APC/C inactivation, we found that BGLF4 stabilizes the expression of many known APC/C substrates. We also noted hyperphosphorylation of 22 proteins associated the nuclear pore complex, which may contribute to nuclear pore disassembly and SAC activation. A drug that inhibits mitotic checkpoint activation also suppressed the accumulation of extracellular EBV virus. Taken together, our data reveal that, in addition to the DDR, manipulation of mitotic kinase signaling and SAC activation are mechanisms associated with lytic EBV replication. All MS data have been deposited in the ProteomeXchange with identifier PXD002411 (http://proteomecentral.proteomexchange.org/dataset/PXD002411).
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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.