ArticleThe Journal of biological chemistry2013
Bromodomain and extraterminal (BET) protein inhibition suppresses human T cell leukemia virus 1 (HTLV-1) Tax protein-mediated tumorigenesis by inhibiting nuclear factor κB (NF-κB) signaling.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 50 citations in OpenAlex.
- BRD proteins in human retroviral infection: emerging evidence from HIV-1 and future perspectives for HTLV-1.Molecular biology reports · 2026Review
- PDLIM2 in Lung Adenocarcinoma Metastasis.bioRxiv : the preprint server for biology · 2025Article
- Advances in epigenetic treatment of adult T-cell leukemia/lymphoma: a comprehensive review.Clinical epigenetics · 2025Review
- BET Protein Inhibitor JQ1 Ameliorates Experimental Peritoneal Damage by Inhibition of Inflammation and Oxidative Stress.Antioxidants (Basel, Switzerland) · 2023Article
- BET in hematologic tumors: Immunity, pathogenesis, clinical trials and drug combinations.Genes & diseases · 2023Review
- Differential responses of pulmonary vascular cells from PAH patients and controls to TNFα and the effect of the BET inhibitor JQ1.Respiratory research · 2023Article
- Bromodomain-containing protein 4 (BRD4): a key player in inflammatory bowel disease and potential to inspire epigenetic therapeutics.Expert opinion on therapeutic targets · 2023Review
- Epigenetic Modulation of Gremlin-1/NOTCH Pathway in Experimental Crescentic Immune-Mediated Glomerulonephritis.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Targeting bromodomain and extra-terminal proteins to inhibit neuroblastoma tumorigenesis through regulating MYCN.Frontiers in cell and developmental biology · 2022Review
- Relevance of BET Family Proteins in SARS-CoV-2 Infection.Biomolecules · 2021Review
- Latency Reversing Agents: Kick and Kill of HTLV-1?International journal of molecular sciences · 2021Review
- Loss of FBXW7-mediated degradation of BRAF elicits resistance to BET inhibitors in adult T cell leukemia cells.Molecular cancer · 2020Article
- BET bromodomain proteins regulate transcriptional reprogramming in genetic dilated cardiomyopathy.JCI insight · 2020Article
- Molecular biology of human T cell leukemia virus.Seminars in diagnostic pathology · 2020Review
- Safety and Efficacy of Bromodomain and Extra-Terminal Inhibitors for the Treatment of Hematological Malignancies and Solid Tumors: A Systematic Study of Clinical Trials.Frontiers in pharmacology · 2020Review
- Pinning Down the Transcription: A Role for Peptidyl-ProlylFrontiers in cell and developmental biology · 2020Review
- Bromodomain and Extraterminal Proteins as Novel Epigenetic Targets for Renal Diseases.Frontiers in pharmacology · 2019Review
- Targeting the HTLV-I-Regulated BATF3/IRF4 Transcriptional Network in Adult T Cell Leukemia/Lymphoma.Cancer cell · 2018Article
- Targeting General Transcriptional Machinery as a Therapeutic Strategy for Adult T-Cell Leukemia.Molecules (Basel, Switzerland) · 2018Review
- BRD4 regulates cellular senescence in gastric cancer cells via E2F/miR-106b/p21 axis.Cell death & disease · 2018Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The etiology of human T cell leukemia virus 1 (HTLV-1)-mediated adult T cell leukemia is associated with the ability of viral oncoprotein Tax to induce sustained NF-κB activation and the expression of many NF-κB target genes. Acetylation of the RelA subunit of NF-κB and the subsequent recruitment of bromodomain-containing factor Brd4 are important for the expression of NF-κB target genes in response to various stimuli. However, their contributions to Tax-mediated NF-κB target gene expression and tumorigenesis remain unclear. Here we report that Tax induced the acetylation of lysine 310 of RelA and the binding of Brd4 to acetylated RelA to facilitate Tax-mediated transcriptional activation of NF-κB. Depletion of Brd4 down-regulated Tax-mediated NF-κB target gene expression and cell proliferation. Inhibiting the interaction of Brd4 and acetylated RelA with the bromodomain extraterminal protein inhibitor JQ1 suppressed the proliferation of Tax-expressing rat fibroblasts and Tax-positive HTLV-1-infected cells and Tax-mediated cell transformation and tumorigenesis. Moreover, JQ1 attenuated the Tax-mediated transcriptional activation of NF-κB, triggering the polyubiquitination and proteasome-mediated degradation of constitutively active nuclear RelA. Our results identify Brd4 as a key regulator for Tax-mediated NF-κB gene expression and suggest that targeting epigenetic regulators such as Brd4 with the bromodomain extraterminal protein inhibitor might be a potential therapeutic strategy for cancers and other diseases associated with HTLV-1 infection.
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