HTLV-1 Tax enhances NF-kappa B2 expression and binds to the products p52 and p100, but does not suppress the inhibitory function of p100.
Tax protein of HTLV-1 triggers transcriptional activation through enhancers, NF-kappa B binding site, 21-bp enhancer, and serum response element. Previously, we demonstrated binding of Tax to transcription factors NF-kappa B1 p105 and p50. Here, we report that Tax enhances expression of NF-kappa B2 at the mRNA level and proteins; the effect was more apparent on the p52 expression than on its precursor p100, suggesting post-translational regulation. Consistent with these observations, HTLV-1-infected T-cell lines expressed higher levels of p52. Tax binds to the protein products p52 and p100 which inhibits NF-kappa B proteins forming cytoplasmic complexes; the binding to p100 was preferential over NF-kappa B1 p105. However, Tax did not induce efficient dissociation of the cytoplasmic complexes p100/c-Rel or p100/p65, and thus did not induce nuclear translocation of c-Rel or p65. This was in sharp contrast to the previous observation that Tax dissociated the p105/c-Rel and I kappa B-gamma/p65 complexes. These results indicate that HTLV-1 Tax interacts with NF-kappa B2 p100 and p52 and upregulate the NF-kappa B function, but their contribution to Tax-mediated transcriptional regulation differs from those of NF-kappa B1.
Department of Cellular and Molecular Biology, University of Tokyo, Japan.
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Murakami
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Hirai
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Suzuki
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Fujisawa
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Yoshida
D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D016356:Gene Products, tax / Q000096:biosynthesis / Q000378:metabolism*; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007668:Kidney; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000096:biosynthesis*; D052003:NF-kappa B p52 Subunit; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D013601:T-Lymphocytes; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D016356:Gene Products, tax; D046911:Macromolecular Substances; D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; D011518:Proto-Oncogene Proteins