Abstract
Human T cell leukemia virus type 1 (HTLV-1) Tax-induced persistent activation of the NF-κB pathway is perceived as the primary cause of adult T cell leukemia (ATL), an aggressive leukemia caused by HTLV-1. Although elevated oncoprotein Bcl-3 levels are found in many HTLV-1-infected T cell lines and ATL cells, the role of Bcl-3 in the malignant progression caused by HTLV-1 retrovirus remains poorly understood. We confirmed, in the present study, that the Tax-induced NF-κB activation involves the regulation of Bcl-3. Both knockdown and overexpression of Bcl-3 inhibit the Tax-induced NF-κB activation. Similarly, excessive Bcl-3 inhibits the NF-κB/DNA binding activity and significantly decreases Tax-induced p65 nuclear translocation. The present results demonstrate the pleiotropic roles of Bcl-3 in Tax-induced NF-κB activation and indicate that a balance in the aberrant Bcl-3 expression may be established to play an important role in the maintenance of proliferation and inhibition of apoptosis in HTLV-1-infected and ATL cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Apoptosis
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B-Cell Lymphoma 3 Protein
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Blotting, Western
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Cell Nucleus / drug effects
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Cell Nucleus / metabolism
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Cell Proliferation
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Cytoplasm / drug effects
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Cytoplasm / metabolism
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Electrophoretic Mobility Shift Assay
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Fluorescent Antibody Technique
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Gene Products, tax / pharmacology*
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Human T-lymphotropic virus 1 / pathogenicity
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Humans
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Leukemia-Lymphoma, Adult T-Cell / genetics
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Leukemia-Lymphoma, Adult T-Cell / metabolism
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Leukemia-Lymphoma, Adult T-Cell / prevention & control*
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / genetics
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NF-kappa B / metabolism*
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Nitriles / pharmacology
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Plasmids / genetics
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Protein Transport
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Proto-Oncogene Proteins / antagonists & inhibitors
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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RNA, Small Interfering / genetics
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Sulfones / pharmacology
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Transcription Factor RelA / metabolism*
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Tumor Cells, Cultured
Substances
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3-(4-methylphenylsulfonyl)-2-propenenitrile
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B-Cell Lymphoma 3 Protein
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BCL3 protein, human
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Gene Products, tax
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NF-kappa B
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Nitriles
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Proto-Oncogene Proteins
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RNA, Small Interfering
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Sulfones
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Transcription Factor RelA
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Transcription Factors