Suppression of signals required for activation of transcription factor NF-kappa B in cells constitutively expressing the HTLV-I Tax protein.
Transient short-term expression of the Tax protein of human T-cell leukemia virus type-I (HTLV-I) leads to activation of the pleiotropic transcription factor NF-kappa B. Consistent with findings obtained with transient expression assays, we observed marked accumulation of the transcription factor NF-kappa B in the nucleus of Namalwa B lymphoid cells, which constitutively express Tax. In contrast, NF-kappa B activity was not detected in the nucleus following long-term expression of Tax in Jurkat T lymphocytes. The ability of both mitogens and cytokines to activate NF-kappa B was also blocked in Jurkat cells constitutively expressing Tax. However, the activation of other mitogen-inducible transcription factors, such as Fos and Jun, was unaffected. Thus, depending on the cellular environment, the short- and long-term effects of Tax expression can be quite different. Consequently, one function of Tax in cells infected with HTLV-I might involve cell-type-specific suppression, as opposed to activation, of distinct signal pathways. The cells lines described here should be useful for the delineation of signaling pathways utilized in the selective regulation of gene expression.
Ruben
S M
SM
Department of Molecular Oncology and Virology, Roche Institute of Molecular Biology, Roche Research Center, Nutley, NJ 07110.
Rosen
C A
CA
D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000378:metabolism*; D005814:Genes, Viral; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D008934:Mitogens / Q000494:pharmacology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D012091:Repetitive Sequences, Nucleic Acid; D015398:Signal Transduction; D014157:Transcription Factors / Q000096:biosynthesis* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014790:Visna-maedi virus / Q000235:genetics
D004268:DNA-Binding Proteins; D016356:Gene Products, tax; D008934:Mitogens; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha