ArticlePLoS pathogens2014
EBNA3C augments Pim-1 mediated phosphorylation and degradation of p21 to promote B-cell proliferation.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 52 citations in OpenAlex.
- Ubiquitination dynamics in human tumour viruses: Viral infection, oncogenesis and antiviral therapy.The FEBS journal · 2026Review
- Decoding microbial carcinogenic strategies: ubiquitination and SUMO modification.Frontiers in microbiology · 2025Review
- Human Viral Oncoproteins and Ubiquitin-Proteasome System.Global medical genetics · 2024Review
- Review
- Pim-1 kinase protects the liver from ischemia reperfusion injury by regulating dynamics-related protein 1.iScience · 2024Article
- How to manage drug-virus interplay underlying skin eruptions in children.The World Allergy Organization journal · 2024Review
- Design, synthesis and cytotoxic evaluation of novel bis-thiazole derivatives as preferential Pim1 kinase inhibitors withJournal of enzyme inhibition and medicinal chemistry · 2023Article
- Review
- AUM302, a novel triple kinase PIM/PI3K/mTOR inhibitor, is a potent in vitro pancreatic cancer growth inhibitor.PloS one · 2023Article
- Pim1 promotes IFN-β production by interacting with IRF3.Experimental & molecular medicine · 2022Article
- Time-resolved transcriptomes reveal diverse B cell fate trajectories in the early response to Epstein-Barr virus infection.Cell reports · 2022Article
- Virus-Mediated Inhibition of Apoptosis in the Context of EBV-Associated Diseases: Molecular Mechanisms and Therapeutic Perspectives.International journal of molecular sciences · 2022Review
- Review
- The Epstein-Barr virus noncoding RNA EBER2 transactivates the UCHL1 deubiquitinase to accelerate cell growth.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Negative Regulation of Erythroid Differentiation via the CBX8-TRIM28 Axis.Molecules and cells · 2021Article
- Novel Pan-Pim Kinase Inhibitors With Imidazopyridazine and Thiazolidinedione Structure Exert Potent Antitumor Activities.Frontiers in pharmacology · 2021Article
- Proteasomal inhibition triggers viral oncoprotein degradation via autophagy-lysosomal pathway.PLoS pathogens · 2020Article
- The role of Pim kinase in immunomodulation.American journal of cancer research · 2020Review
- Polyploid Giant Cancer Cells, a Hallmark of Oncoviruses and a New Therapeutic Challenge.Frontiers in oncology · 2020Review
- Viral Infections and Cutaneous Drug-Related Eruptions.Frontiers in pharmacology · 2020Review
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Epstein-Barr virus (EBV), a ubiquitous human herpesvirus, can latently infect the human population. EBV is associated with several types of malignancies originating from lymphoid and epithelial cell types. EBV latent antigen 3C (EBNA3C) is essential for EBV-induced immortalization of B-cells. The Moloney murine leukemia provirus integration site (PIM-1), which encodes an oncogenic serine/threonine kinase, is linked to several cellular functions involving cell survival, proliferation, differentiation, and apoptosis. Notably, enhanced expression of Pim-1 kinase is associated with numerous hematological and non-hematological malignancies. A higher expression level of Pim-1 kinase is associated with EBV infection, suggesting a crucial role for Pim-1 in EBV-induced tumorigenesis. We now demonstrate a molecular mechanism which reveals a direct role for EBNA3C in enhancing Pim-1 expression in EBV-infected primary B-cells. We also showed that EBNA3C is physically associated with Pim-1 through its amino-terminal domain, and also forms a molecular complex in B-cells. EBNA3C can stabilize Pim-1 through abrogation of the proteasome/Ubiquitin pathway. Our results demonstrate that EBNA3C enhances Pim-1 mediated phosphorylation of p21 at the Thr145 residue. EBNA3C also facilitated the nuclear localization of Pim-1, and promoted EBV transformed cell proliferation by altering Pim-1 mediated regulation of the activity of the cell-cycle inhibitor p21/WAF1. Our study demonstrated that EBNA3C significantly induces Pim-1 mediated proteosomal degradation of p21. A significant reduction in cell proliferation of EBV-transformed LCLs was observed upon stable knockdown of Pim-1. This study describes a critical role for the oncoprotein Pim-1 in EBV-mediated oncogenesis, as well as provides novel insights into oncogenic kinase-targeted therapeutic intervention of EBV-associated cancers.
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