Identification of a novel cyclosporin-sensitive element in the human tumor necrosis factor alpha gene promoter

doi:10.1084/jem.178.4.1365

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Identification of a novel cyclosporin-sensitive element in the human tumor necrosis factor alpha gene promoter

AE Goldfeld, PG McCaffrey, JL Strominger and A Rao
Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02114.

Tumor necrosis factor alpha (TNF-alpha), a cytokine with pleiotropic biological effects, is produced by a variety of cell types in response to induction by diverse stimuli. In this paper, TNF-alpha mRNA is shown to be highly induced in a murine T cell clone by stimulation with T cell receptor (TCR) ligands or by calcium ionophores alone. Induction is rapid, does not require de novo protein synthesis, and is completely blocked by the immunosuppressant cyclosporin A (CsA). We have identified a human TNF-alpha promoter element, kappa 3, which plays a key role in the calcium-mediated inducibility and CsA sensitivity of the gene. In electrophoretic mobility shift assays, an oligonucleotide containing kappa 3 forms two DNA protein complexes with proteins that are present in extracts from unstimulated T cells. These complexes appear in nuclear extracts only after T cell stimulation. Induction of the inducible nuclear complexes is rapid, independent of protein synthesis, and blocked by CsA, and thus, exactly parallels the induction of TNF-alpha mRNA by TCR ligands or by calcium ionophore. Our studies indicate that the kappa 3 binding factor resembles the preexisting component of nuclear factor of activated T cells. Thus, the TNF-alpha gene is an immediate early gene in activated T cells and provides a new model system in which to study CsA-sensitive gene induction in activated T cells.
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Hayes, A. L., Smith, C., Foxwell, B. M. J., Brennan, F. M. (1999). CD45-induced Tumor Necrosis Factor alpha Production in Monocytes Is Phosphatidylinositol 3-Kinase-dependent and Nuclear Factor-kappa B-independent. J. Biol. Chem. 274: 33455-33461 [Abstract] [Full Text]
Azzawi, M., Hasleton, P. (1999). Tumour necrosis factor alpha and the cardiovascular system: its role in cardiac allograft rejection and heart disease. Cardiovasc Res 43: 850-859 [Full Text]
Marshall, W. L., Brinkman, B. M. N., Ambrose, C. M., Pesavento, P. A., Uglialoro, A. M., Teng, E., Finberg, R. W., Browning, J. L., Goldfeld, A. E. (1999). Signaling Through the Lymphotoxin-{beta} Receptor Stimulates HIV-1 Replication Alone and in Cooperation with Soluble or Membrane-Bound TNF-{alpha}. J. Immunol. 162: 6016-6023 [Abstract] [Full Text]
Lobo, F. M., Zanjani, R., Ho, N., Chatila, T. A., Fuleihan, R. L. (1999). Calcium-Dependent Activation of TNF Family Gene Expression by Ca2+/Calmodulin Kinase Type IV/Gr and Calcineurin. J. Immunol. 162: 2057-2063 [Abstract] [Full Text]
Hoffmeyer, A., Grosse-Wilde, A., Flory, E., Neufeld, B., Kunz, M., Rapp, U. R., Ludwig, S. (1999). Different Mitogen-activated Protein Kinase Signaling Pathways Cooperate to Regulate Tumor Necrosis Factor alpha �Gene Expression in T Lymphocytes. J. Biol. Chem. 274: 4319-4327 [Abstract] [Full Text]
Sweetser, M. T., Hoey, T., Sun, Y.-L., Weaver, W. M., Price, G. A., Wilson, C. B. (1998). The Roles of Nuclear Factor of Activated T Cells and Ying-Yang 1�in Activation-induced Expression of the Interferon-gamma Promoter in T Cells. J. Biol. Chem. 273: 34775-34783 [Abstract] [Full Text]
Mages, H. W., Baag, R., Steiner, B., Kroczek, R. A. (1998). Utilization of an NF-ATp Binding Promoter Element for EGR3 Expression in T Cells but Not Fibroblasts Provides a Molecular Model for the Lymphoid Cell-Specific Effect of Cyclosporin A. Mol. Cell. Biol. 18: 7157-7165 [Abstract] [Full Text]
Rosen, T., Krikun, G., Ma, Y., Wang, E.-Y., Lockwood, C. J., Guller, S. (1998). Chronic Antagonism of Nuclear Factor-{kappa}B Activity in Cytotrophoblasts by Dexamethasone: A Potential Mechanism for Antiinflammatory Action of Glucocorticoids in Human Placenta. J. Clin. Endocrinol. Metab. 83: 3647-3652 [Abstract] [Full Text]
Ballester, A., Velasco, A., Tobena, R., Alemany, S. (1998). Cot Kinase Activates Tumor Necrosis Factor-alpha Gene Expression in a Cyclosporin A-resistant Manner. J. Biol. Chem. 273: 14099-14106 [Abstract] [Full Text]
Zagariya, A., Mungre, S., Lovis, R., Birrer, M., Ness, S., Thimmapaya, B., Pope, R. (1998). Tumor Necrosis Factor Alpha Gene Regulation: Enhancement of C/EBPbeta -Induced Activation by c-Jun. Mol. Cell. Biol. 18: 2815-2824 [Abstract] [Full Text]
Hata, D., Kitaura, J., Hartman, S. E., Kawakami, Y., Yokota, T., Kawakami, T. (1998). Bruton's Tyrosine Kinase-mediated Interleukin-2 Gene Activation in Mast Cells. DEPENDENCE ON THE c-Jun N-TERMINAL KINASE ACTIVATION PATHWAY. J. Biol. Chem. 273: 10979-10987 [Abstract] [Full Text]
Hata, D., Kawakami, Y., Inagaki, N., Lantz, C. S., Kitamura, T., Khan, W. N., Maeda-Yamamoto, M., Miura, T., Han, W., Hartman, S. E., Yao, L., Nagai, H., Goldfeld, A. E., Alt, F. W., Galli, S. J., Witte, O. N., Kawakami, T. (1998). Involvement of Bruton's Tyrosine Kinase in Fcepsilon RI-dependent Mast Cell Degranulation and Cytokine Production. JEM 187: 1235-1247 [Abstract] [Full Text]
Amasaki, Y., Masuda, E. S., Imamura, R., Arai, K.-i., Arai, N. (1998). Distinct NFAT Family Proteins Are Involved in the Nuclear NFAT-DNA Binding Complexes from Human Thymocyte Subsets. J. Immunol. 160: 2324-2333 [Abstract] [Full Text]
Holtz-Heppelmann, C. J., Algeciras, A., Badley, A. D., Paya, C. V. (1998). Transcriptional Regulation of the Human FasL Promoter-Enhancer Region. J. Biol. Chem. 273: 4416-4423 [Abstract] [Full Text]
Wong, B. R., Rho, J., Arron, J., Robinson, E., Orlinick, J., Chao, M., Kalachikov, S., Cayani, E., Bartlett III, F. S., Frankel, W. N., Lee, S. Y., Choi, Y. (1997). TRANCE Is a Novel Ligand of the Tumor Necrosis Factor Receptor Family That Activates c-Jun N-terminal Kinase in T Cells. J. Biol. Chem. 272: 25190-25194 [Abstract] [Full Text]
Beals, C R, Clipstone, N A, Ho, S N, Crabtree, G R (1997). Nuclear localization of NF-ATc by a calcineurin-dependent, cyclosporin-sensitive intramolecular interaction.. Genes Dev. 11: 824-834 [Abstract]
Beals, C. R., Sheridan, C. M., Turck, C. W., Gardner, P., Crabtree, G. R. (1997). Nuclear Export of NF-ATc Enhanced by Glycogen Synthase Kinase-3. Science 275: 1930-1933 [Abstract] [Full Text]
Handen, J. S., Rosenberg, H. F. (1997). Intronic Enhancer Activity of the Eosinophil-derived Neurotoxin (RNS2) and Eosinophil Cationic Protein (RNS3) Genes Is Mediated by an NFAT-1 Consensus Binding Sequence. J. Biol. Chem. 272: 1665-1669 [Abstract] [Full Text]
Hodge, M. R., Chun, H. J., Rengarajan, J., Alt, A., Lieberson, R., Glimcher, L. H. (1996). NF-AT-Driven Interleukin-4 Transcription Potentiated by NIP45. Science 274: 1903-1905 [Abstract] [Full Text]
Kwon, J., Lee, S. J., Benveniste, E. N. (1996). A 3' cis-Acting Element Is Involved in Tumor Necrosis Factor-alpha Gene Expression in Astrocytes. J. Biol. Chem. 271: 22383-22390 [Abstract] [Full Text]
Park, J., Takeuchi, A., Sharma, S. (1996). Characterization of a New Isoform of the NFAT (Nuclear Factor of Activated T Cells) Gene Family Member NFATc. J. Biol. Chem. 271: 20914-20921 [Abstract] [Full Text]
Wesselborg, S., Fruman, D. A., Sagoo, J. K., Bierer, B. E., Burakoff, S. J. (1996). Identification of a Physical Interaction between Calcineurin and Nuclear Factor of Activated T Cells (NFATp). J. Biol. Chem. 271: 1274-1277 [Abstract] [Full Text]
Park, J., Yaseen, N. R., Hogan, P. G., Rao, A., Sharma, S. (1995). Phosphorylation of the Transcription Factor NFATp Inhibits Its DNA Binding Activity in Cyclosporin A-treated Human B and T Cells. J. Biol. Chem. 270: 20653-20659 [Abstract] [Full Text]
Ho, S. N., Thomas, D. J., Timmerman, L. A., Li, X., Francke, U., Crabtree, G. R. (1995). NFATc3, a Lymphoid-specific NFATc Family Member That Is Calcium-regulated and Exhibits Distinct DNA Binding Specificity. J. Biol. Chem. 270: 19898-19907 [Abstract] [Full Text]
Kr�mer, B., Wiegmann, K., Kr�nke, M. (1995). Regulation of the Human TNF Promoter by the Transcription Factor Ets. J. Biol. Chem. 270: 6577-6583 [Abstract] [Full Text]
Jain, J., Burgeon, E., Badalian, T. M., Hogan, P. G., Rao, A. (1995). A Similar DNA-binding Motif in NFAT Family Proteins and the Rel Homology Region. J. Biol. Chem. 270: 4138-4145 [Abstract] [Full Text]
McCaffrey, P., Luo, C, Kerppola, T., Jain, J, Badalian, T., Ho, A., Burgeon, E, Lane, W., Lambert, J., Curran, T, et, al. (1993). Isolation of the cyclosporin-sensitive T cell transcription factor NFATp. Science 262: 750-754 [Abstract]
Yan Liu, X., Robinson, D., Veach, R. A., Liu, D., Timmons, S., Collins, R. D., Hawiger, J. (2000). Peptide-directed Suppression of a Pro-inflammatory Cytokine Response. J. Biol. Chem. 275: 16774-16778 [Abstract] [Full Text]