ArticlePLoS pathogens2014
Epstein-Barr virus down-regulates tumor suppressor DOK1 expression.
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 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
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- CBX2 enhances the progression and TMZ chemoresistance of glioma via EZH2-mediated epigenetic silencing of PTEN expression.Frontiers in pharmacology · 2024Article
- Histone methylation in Epstein-Barr virus-associated diseases.Epigenomics · 2024Review
- EZH2 abnormalities in lymphoid malignancies: underlying mechanisms and therapeutic implications.Journal of hematology & oncology · 2019Review
- Molecular mechanisms of EBV-driven cell cycle progression and oncogenesis.Medical microbiology and immunology · 2019Review
- Insulin and insulin-like growth factors act as renal cell cancer intratumoral regulators.Journal of cell communication and signaling · 2019Article
- Epstein-Barr Virus-Induced Epigenetic Pathogenesis of Viral-Associated Lymphoepithelioma-Like Carcinomas and Natural Killer/T-Cell Lymphomas.Pathogens (Basel, Switzerland) · 2018Review
- Inhibition of demethylase KDM6B sensitizes diffuse large B-cell lymphoma to chemotherapeutic drugs.Haematologica · 2017Article
- Manipulation of the host cell membrane by human γ-herpesviruses EBV and KSHV for pathogenesis.Virologica Sinica · 2016Review
- Higher methylation intensity induced by EBV LMP1 via NF-κB/DNMT3b signaling contributes to silencing of PTEN gene.Oncotarget · 2016Article
- Subcellular compartmentalization of docking protein-1 contributes to progression in colorectal cancer.EBioMedicine · 2016Article
- An epigenetic view of B-cell disorders.Immunology and cell biology · 2015Review
- Oncogenic induction of cellular high CpG methylation by Epstein-Barr virus in malignant epithelial cells.Chinese journal of cancer · 2014Article
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Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The DOK1 tumor suppressor gene encodes an adapter protein that acts as a negative regulator of several signaling pathways. We have previously reported that DOK1 expression is up-regulated upon cellular stress, via the transcription factor E2F1, and down-regulated in a variety of human malignancies due to aberrant hypermethylation of its promoter. Here we show that Epstein Barr virus (EBV) infection of primary human B-cells leads to the down-regulation of DOK1 gene expression via the viral oncoprotein LMP1. LMP1 alone induces recruitment to the DOK1 promoter of at least two independent inhibitory complexes, one containing E2F1/pRB/DNMT1 and another containing at least EZH2. These events result in tri-methylation of histone H3 at lysine 27 (H3K27me3) of the DOK1 promoter and gene expression silencing. We also present evidence that the presence of additional EBV proteins leads to further repression of DOK1 expression with an additional mechanism. Indeed, EBV infection of B-cells induces DNA methylation at the DOK1 promoter region including the E2F1 responsive elements that, in turn, lose the ability to interact with E2F complexes. Treatment of EBV-infected B-cell-lines with the methyl-transferase inhibitor 5-aza-2'-deoxycytidine rescues DOK1 expression. In summary, our data show the deregulation of DOK1 gene expression by EBV and provide novel insights into the regulation of the DOK1 tumor suppressor in viral-related carcinogenesis.
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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.