NF-κB: A Mediator of Pathogen and Stress Responses

  • Ulrich Siebenlist
  • Keith Brown
  • Guido Franzoso
Part of the Progress in Gene Expression book series (PRGE)


The transcription factor NF-κB is a central regulator of defensive responses which are mounted by cells against many potentially threatening environmental challenges. Bacteria, viruses, parasites, injury, radiation, oxidative stress, numerous chemical agents and many cytokines released in response to such challenges are all well-studied and potent activators of this transcription factor in a number of different cell types. Activated NF-κB then induces the expression of many genes whose encoded functions play critical roles for the defense of the organism. The induced proteins have a wide range of activities, including antibacterial or anti-viral functions, antigen recognition, cellular migration and adhesion as well as hematopoietic cell differentiation and proliferation. Aside from regulating cellular genes, several viruses, including the human immunodeficiency virus, have diverted this factor for their own purposes. Since many cytokines are regulated by NF-κB, this transcription factor appears critical to a coordinated defense response. In an evolutionary sense, the association between defensive responses and NF-κB dates at least as far back as insects.


Human Immunodeficiency Virus Human Immunodeficiency Virus Type Chicken Embryo Fibroblast Ankyrin Domain Bours Versus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abbadie C, Kabrun N, Bouali F, Smardova, J, Stehelin D, Bandenbunder B, Enrietto PJ (1993): High levels of c-rel expression are associated with programmed cell death in the developing avian embryo and in bone marrow cells in vitro. Cell 75: 899–912PubMedGoogle Scholar
  2. Abdollahi A, Lord KA, Hoffman-Liebermann B, Liebermann D (1991): Interferon regulatory factor 1 is a myeloid differentiation primary response gene induced by interleukin 6 and leukemia inhibitory factor: role in growth inhibition. Cell Growth Differ 2: 401–407PubMedGoogle Scholar
  3. Andalibi A, Liao F, Imes S, Fogelman AM, Lusis AJ (1993): Oxidized lipoproteins influence gene expression by causing oxidative stress and activating the transcription factor NF-κB. Biochem Soc Trans 21: 651–655PubMedGoogle Scholar
  4. Anisowicz A, Messineo M, Lee SW, Sager R (1991): An NF-jcB-like transcription factor mediates IL-1/TNF-α induction of gro in human fibroblasts. J Immunol 147: 520–527PubMedGoogle Scholar
  5. Arima N, Molitor JA, Smith MR, Kim JH (1991): Human T-cell leukemia virus type I Tax induces expression of the Rel-related family of kB enhancer-binding proteins: evidence for a pretranslational component of regulation. J Virol 65: 6892–6899PubMedGoogle Scholar
  6. Bachelerie F, Alcami J, Arenzana-Seisdedos F, Virelizier J-L (1991): HIV enhancer activity perpetuated by NF-kB induction on infection of monocytes. Nature 350: 709–712PubMedGoogle Scholar
  7. Baeuerle PA (1991): The inducible transcription activator NF-κB: regulation by distinct protein subunits. Biochem Biophys Acta 1072: 63–80PubMedGoogle Scholar
  8. Baeuerle PA, Baltimore D (1988): IκB: a specific inhibitor of the NF-κB transcription factor. Science 242: 540–546PubMedGoogle Scholar
  9. Baeuerle PA, Henkel T (1994): Function and activation of NF-κB in the immune system. Annu Rev Immunol 12: 141–179PubMedGoogle Scholar
  10. Bakalkin GYA, Yakovleva T, Terenius L (1993: NF-κB-like factors in the murine brain. Developmentally-regulated and tissue-specific expression. Mol Brain Res 20:137–146PubMedGoogle Scholar
  11. Baldwin AJ, Azizkhan JC, Jensen DE, Beg AA, Coodly LR (1991): Induction of NF-κB DNA-binding activity during the GO to Gl transition in mouse fibroblasts. Mol Cell Biol 11: 4943–4951PubMedGoogle Scholar
  12. Ballard DW, Dixon EP, Peffer NJ, Bogerd H, Doerre S, Stein B, Greene WC (1992): The 65-kDa subunit of human NF-κB functions as a potent transcriptional activator and a target for v-Rel-mediated repression. Proc Natl Acad Sci USA 89: 1875–1879PubMedGoogle Scholar
  13. Ballard DW, Walker WH, Doerre S, Sista P, Molitor JA, Dixon EP, Peffer NJ, Hannink M, Greene WC (1990): The V-REL oncogene encodes a κB enhancer binding protein that inhibits NF-kB function. Cell 63: 803–814PubMedGoogle Scholar
  14. Beg AA, Baldwin AS (1993): The IκB proteins: multifunctional regulators of Rel/NF-κB Transcription factors. Genes Dev 7: 2064–2070PubMedGoogle Scholar
  15. Beg AA, Finco TS, Nantermet PV Baldwin AS (1993): Tumor necrosis factor and interleukin-1 lead to phosphorylation and loss of IκB α: a mechanism for NF-κB activation. Mol Cell Biol 13: 3301–3310PubMedGoogle Scholar
  16. Beg AA, Ruben SM, Scheinman RI, Haskill S, Rosen CA, Baldwin AS (1992): IκB interacts with the nuclear localization sequences of the subunits of NF-κB: a mechanisms for cytoplasmic retention. Genes Dev 6: 1899–1913PubMedGoogle Scholar
  17. Bellas RE, Hopkins N, Li Y (1993): The NF-κB binding site is necessary for efficient replication of simian immunodeficiency virus of macaques in primary macrophages but not in T cells in vitro. J Virol 67: 2908–2913PubMedGoogle Scholar
  18. Beraud C, Sun SC, Ganchi P, Ballard DW, Green WC (1994): Human T-cell leukemia virus type I tax associates with and is negatively regulated by the NF-κB2 p100 gene product: implications for viral latency. Mol Cell Biol 14: 1374–1382PubMedGoogle Scholar
  19. Betts JC, Cheshire JK, Akira S, Kishimoto T, Woo P (1993): The role of NF-κB and NF-IL-6 transactivating factors in the synergistic activation of human serum amyloid A gene expression by interleukin-1 and interleukin-6. J Biol Chem 268: 25624–25631PubMedGoogle Scholar
  20. Bhatia K, Huppi K, McKeithan T, Siwarski D (1991): Mouse bcl-3: cDNA structure, mapping and stage-dependent expression in B lymphocytes. Oncogene 6: 1569–1573PubMedGoogle Scholar
  21. Blank V, Kourilsky P, Israël A (1991): Cytoplasmic retention, DNA binding and processing of the NF-κB p50 precursor are controlled by a small region in its C-terminus. EMBO J 10: 4159–4167PubMedGoogle Scholar
  22. Blank V, Kourilsky P, Israël A (1992): NF-κB and related proteins: Rel/dorsal homologies meet ankyrin-like repeats. Trends Biochem Sci 17: 135–140PubMedGoogle Scholar
  23. Boehmelt G, Walker A, Kabrun N, Melitzer G, Beug H, Zenke M (1992): Hormone-regulated v-rel estrogen receptor fusion protein: reversible induction of cell transformation and cellular gene expression. EMBO J 11: 4641–4652PubMedGoogle Scholar
  24. Boldogh I, Fons MP, Albrecht T (1993): Increased levels of sequence-specific DNA-binding proteins in human cytomegalovirus-infected cells. Biochem Biophys Res Commun 197: 1505–1510PubMedGoogle Scholar
  25. Bomsztyk K, Rooney JW, Iwasaki T, Rachi NA, Dower SK, Sibley C (1991): Evidence that interleukin-1 and phorbolesters activate NF-κB by different pathways: of protein kinase C. Cell Regul 2: 329–335PubMedGoogle Scholar
  26. Bose HJ (1992): The Rel family: models for transcriptional regulation and oncogenic transformation. Biochim Biophys Acta 1114: 1–17PubMedGoogle Scholar
  27. Bours V, Azarenko V, Dejardin E, Siebenlist U (1994): Human RelB (I-Rel) functions as a κB site-dependent transactivating member of the family of Rel-related proteins. Oncogene: in pressGoogle Scholar
  28. Bours V, Burd PR, Brown K, Villalobos J, Park S, Ryseck R, Bravo R, Kelly K, Siebenlist U (1992a): A novel mitogen-inducible gene product related the p50-p105-NF-κB participates in transactivation through a κB site. Mol Cell Biol 12: 685–695PubMedGoogle Scholar
  29. Bours V, Franzoso G, Brown K, Park S, Azarenko V, Tomita-Yamaguchi M, Kelly K, Siebenlist U (1992b): Lymphocyte activation and the family of NF-κB transcription factor complexes. Curr Topics Microbiol Immunol 182: 411–420Google Scholar
  30. Bours V, Franzoso G, Azarenko V, Park S, Kanno T, Brown K, Siebenlist U (1993): The oncoprotein Bcl-3 directly transactivates through κB motifs via association with DNA-binding p50B homodimers. Cell 72: 729–739PubMedGoogle Scholar
  31. Bours V, Villalobos J, Burd PR, Kelly K, Siebenlist U (1990): Cloning of a mitogen-inducible gene encoding a κB DNA-binding protein with homology to the rel oncogene and to cell-cycle motifs. Nature 348: 76–80PubMedGoogle Scholar
  32. Brach MA, Gruss HJ, Kaisho T, Asano Y (1993): Ionizing radiation induces expression of interleukin 6 by human fibroblasts involving activation of nuclear factor-kappa B. J Biol Chem 268: 8466–8472PubMedGoogle Scholar
  33. Bressler P, Brown K, Timmer W, Bours V, Siebenlist U, Fauci AS (1993): Mutational analysis of the p50 subunit of NF-κB and inhibition of NF-κB activity by trans-dominant p50 mutants. J Virol 67: 288–293PubMedGoogle Scholar
  34. Bressler P, Pantaleo G, Demaria A, Fauci AS (1991): Anti-CD2 receptor antibodies activate the HIV long terminal repeat in T lymphocytes. J Immunol 147: 2290–2294PubMedGoogle Scholar
  35. Brown K, Siebenlist U (1994): unpublished observationGoogle Scholar
  36. Brown K, Park S, Kanno T, Franzoso G, Siebenlist U (1993): Mutual regulation of the transcriptional activator NF-κB and its inhibitor, I kappa B-α. Proc Natl Acad Sci USA 90: 2532–2536PubMedGoogle Scholar
  37. Brownell E, Mathieson B, Young Ha, Keller J, Ihle JN, Rice NR (1987): Detection of c-rel-related transcripts in mouse hematopoietic tissues, fractionated lymphocyte populations, and cell lines. Mol Cell Biol 7: 1304–1309PubMedGoogle Scholar
  38. Brownell E, Mittereder N, Rice NR (1989): A human rel protooncogene cDNA containing an Alu fragment as a potential coding exon. Oncogene 4: 935–942PubMedGoogle Scholar
  39. Bruder JT, Heidecker G, Tan T-H, Weske JC, Derse D, Rapp UR (1993): Oncogene activation of HIV-LTR-driven expression via the NF-κB binding sites. Nucl Acids Res 21: 5229–5234PubMedGoogle Scholar
  40. Bull P, Hunter T, Verma IM (1989): Transcriptional induction of the murine c-rel gene with serum and phorbol-12-myristate-13-acetate in fibroblasts. Mol Cell Biol 9: 5239–5243PubMedGoogle Scholar
  41. Bull P, Morley KL, Hoekstra MF, Hunter T, Verma IM (1990): The mouse c-rel protein has an N-terminal regulatory domain and a C-terminal transcriptional trans-activation domain. Mol Cell Biol 10: 5473–5485PubMedGoogle Scholar
  42. Capobianco AJ, Gilmore TD (1991): Repression of a the chicken c-rel promoter by v-Rel in chicken embryo fibroblasts is not mediated through a consensus NF-κB binding site. Oncogene 6: 2203–2210PubMedGoogle Scholar
  43. Capobianco AJ, Simmons DL, Gilmore TD (1990): Cloning and expression of a chicken c-rel cDNA: unlike p69v-rel, p68c-rel is a cytoplasmic protein in chicken embryonic fibroblasts. Oncogene 5: 257–265PubMedGoogle Scholar
  44. Carrasco D, Ryseck R-P, Bravo R (1993): Expression of rel/B transcripts during lymphoid organ development: specific expression in dendritic antigen-presenting cells. Development 118: 1221–1231PubMedGoogle Scholar
  45. Chang CC, Zhang J, Lombardi L, Neri A, Dalla-Favera R (1994): Mechanism of expression and role in transcriptional control of the proto-oncogene NF-κB-2/lyt-10. Oncogene 9:923–933PubMedGoogle Scholar
  46. Chen Y-Y, Wang LC, Huang MS, Rosenberg N (1994): An active v-able protein tyrosine kinase blocks immunoglobulin light-chain gene rearrangement. Genes Dev 8: 688–697PubMedGoogle Scholar
  47. Chiao PJ, Miyamoto S, Verma IM (1994): Autoregulation of IκB-α activity. Proc Natl Acad Sci USA 91: 28–32PubMedGoogle Scholar
  48. Coleman TA, Kunsch C, Maher M, Ruben SM, Rosen CA (1993): Acquisition of NF-κB1 -selective DNA binding by substitution of four amino acid residues from NF-κB1 into RelA. Mol Cell Biol 13: 3850–3859PubMedGoogle Scholar
  49. Collins T (1993): Biology of Disease. Endothelial nuclear factor-κB and the initiation of the atherosclerotic lesion. Lab Invest 68: 499–506PubMedGoogle Scholar
  50. Cordle SR, Donald R, Read MA, Hawiger J (1993): Lipopolysaccharide induces phosphorylation of MAD3 and activation of c-Rel and related NF-κB proteins in human monocytic THP-1 cells. J Biol Chem 268: 268: 11803–11810PubMedGoogle Scholar
  51. Costello R, Lipcey C, Algarte M, Cerdan C, Baeuerle PA, Olive D, Imbert J (1993): Activation of primary human T-lymphocytes through CD2 plus CD28 adhesion molecules induces long-term nuclear expression of NF-κB. Cell Growth Diff 4: 329–339PubMedGoogle Scholar
  52. Cressman DE, Taub R (1993): IκB alpha can localize in the nucleus but shows no direct transactivation potential. Oncogene 8: 2567–2573PubMedGoogle Scholar
  53. Danoff TM, Lalley PA, Chang YS, Heeger PS, Neilson EG (1994): Cloning, genomic organization, and chromosomal localization of the scya5 gene encoding the murine chemokine RANTES. J Immunol 152: 1182PubMedGoogle Scholar
  54. Davis N, Bargmann W, Lim M-Y, Bose H (1990): Avian reticuloendotheliosis virus-transformed lymphoid cells contain multiple pp59v-rel complexes. J Virol 64: 584–591PubMedGoogle Scholar
  55. Davis N, Ghosh S, Simmons DL, Tempst P, Liou H, Baltimore D, Bose HR (1992): Rel-associated pp40: an inhibitor of the rel family of transcription factors. Science 253: 1268–1271Google Scholar
  56. Dbaibo GS, Obeid LM, Hannun YA (1993): Tumor necrosis factor-alpha (TNF-α) signal transduction through ceramid. Dissociation of growth inhibitor effects of TNF-a from activation of nuclear factor-kappa B. J Biol Chem 268: 17762–17766PubMedGoogle Scholar
  57. Deisher TA, Haddix TL, Montgomery KF, Pohlman TH, Kaushansky K, Harlan JM (1993): The role of protein kinase C in the induction of VCAM-1 expression on human umbilical vein endothelial cells. FEBS Lett 331: 285–290PubMedGoogle Scholar
  58. deMartin R, Vanhove B, Cheng Q, Hofer E, Csizmadia V, Winkler H, Bach FH (1993): Cytokine-inducible expression in endothelial cells of an IκB-α-like gene is regulated by NF-κB. EMBO J 12: 2773–2779Google Scholar
  59. Devary Y, Rosette C, DiDonato JA, Karin M (1993): NF-κB activation by ultraviolet light not dependent on a nuclear signal. Science 261: 1442–1445PubMedGoogle Scholar
  60. Diaz-Meco MT, Berra E, Municio MM, Sanz L, Lozano J, Dominguez I, Diaz-Golpe V, Lera MTLd, Alcami J, Paya CV, Arenzana-Seisdedos F, Virelizier J-L, Moscat J (1993): A dominant negative protein kinase c zeta subspecies blocks NF-κB activation. Mol Cell Biol 13: 4770–4775PubMedGoogle Scholar
  61. Diehl JA, McKinsey TA, Hannink M (1993): Differential pp40/IκB-β inhibition of DNA binding by rel proteins. Mol Cell Biol 13: 1769–1778PubMedGoogle Scholar
  62. Dobrzanski P, Ryseck R-P, Bravo R (1993): Both N- and C-terminal domains of RelB are required for full transactivation: role of the N-terminal leucine zipperlike motif. Mol Cell Biol 13: 1572–1482PubMedGoogle Scholar
  63. Doerre S, Sista P, Sun S-C, Ballard DW, Greene WC (1993): The c-rel protooncogene product represses NF-kB p65-mediated transcriptional activation of the long terminal repeat of type 1 human immunodeficiency virus. Proc Natl Acad Sci USA 90: 1023–1027PubMedGoogle Scholar
  64. Dokter WHA, Dijkstra AJ, Koopmans SB, Stulp BK, Keck W, Halie MR, Vellenga E (1994): G(Anh)MTetra, a natural bacterial cell wall breakdown product, induces interleuken-1β and interleuken-6 expression in human monocytes. J Biol Chem 269:4201–4206PubMedGoogle Scholar
  65. Dressler KA, Mathias S, Kolesnick RN (1992): Tumor necrosis factor-alpha activates the sphinjonyelin signal transduction pathway in a cell-free system. Science 255: 1715–1718PubMedGoogle Scholar
  66. Drew P, Ozato K (1994): personal communicationGoogle Scholar
  67. Du W, Maniatis T (1992): An ATF/CREB binding site is required for virus induction of the human interferon beta gene. Proc Natl Acad Sci USA 89: 2150–2154PubMedGoogle Scholar
  68. Du W, Thanos D, Maniatis T (1993): Mechanisms of transcriptional synergism between distinct virus-inducible enhancer elements. Cell 74: 887–898PubMedGoogle Scholar
  69. Duyao MP, Buckler AJ, Sonenshein GE (1990): Interaction of an NF-κB-like factor with a site upstream of the c-myc promoter. Proc Natl Acad Sci USA 87:4727–4731PubMedGoogle Scholar
  70. Duyao MP, Kessler DJ, Spicer DB, Batholomew C, Cleveland JL, Siekevitz M, Sonenshein GE (1992): Transactivation of the c-myc promoter by human T cell leukemia virus type 1 tax is mediated by NF-κB. J Biol Chem 267: 16288–16291PubMedGoogle Scholar
  71. Dyer RB, Collaco CR, Niesei DW, Herzog NK (1993): Shigella flexneri invasion of HeLa cells induces NF-κB DNA-binding activity. Infect Immun 61: 4427–4433PubMedGoogle Scholar
  72. Eck SL, Perkins ND, Carr DP, Nabel GJ (1993): Inhibition of phorbol ester-induced cellular adhesion by competitive binding of NF-κB B in vivo. Mol Cell Biol 13: 6530–6506PubMedGoogle Scholar
  73. Embretson J, Zupancic M, Ribas JL, Burke A (1993): Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS. Nature 362: 359–362PubMedGoogle Scholar
  74. Fan CM, Maniatis T (1991): Generation of p50 subunit of NF-κB by processing of pl05 through an ATP-dependent pathway. Nature 354: 395–398PubMedGoogle Scholar
  75. Feuillard J, Gouy H, Bismuth G, Lee LM (1991): NF-kappa B activation by tumor necrosis factor alpha in the Jurkat T cell line is independent of protein kinase A, protein kinase C, and Ca(2 +)-regulated kinases. Cytokine 3: 257–265PubMedGoogle Scholar
  76. Feuillard J, Korner M, Fourcade C, Costa A (1994): Visualization of the endogenous NF-κB p50 subunit in the nucleus of follicular dendritic cells in germinal centers. J Immunol 152: 12–21PubMedGoogle Scholar
  77. Finco TS, Baldwin AS (1993): κB site dependent induction of gene expression by diverse inducers of nuclear factor κB requires Raf-1. J Bio Chem 24: 17676–17679Google Scholar
  78. Fracchiolla NS, Lombardi L, Slaina M, Migliazzi A, Baldini L, Berti E, Cro L, Polli E, Maiolo AT, Neri A (1993): Structural alterations of the NF-κB transcription factor lyt-10 in lymphoid malignancies. Oncogene 8: 2839–2845PubMedGoogle Scholar
  79. Frantz B, Nordby EC, Bren G, Steffan N, Paya CV, Kincaid RL, Tocci MJ, O’Keefe SJ, O’Neill EA (1994): Calcineurin acts in synergy with PMA to inactivate IκB/ MAD3, an inhibitor of NF-κB. EMBO J 13: 861–870PubMedGoogle Scholar
  80. Franzoso G, Siebenlist U (1994): unpublished observationsGoogle Scholar
  81. Franzoso G, Bours V, Park S, Tomita-Yamaguchi M, Kelly K and Siebenlist U (1992): The candidate oncoprotein Bcl-3 is an antagonist of p50/NF-κB-mediated inhibition. Nature 359: 339–342PubMedGoogle Scholar
  82. Franzoso G, Bours V, Azarenko V, Park S, Tomita-Yamaguchi M, Kanno T, Brown K, Siebenlist U (1993): The oncoprotein Bcl-3 can facilitate NF-κB-mediated transactivation by removing inhibiting p50 homodimers from select κB sites. EMBO J 12:3893–3901PubMedGoogle Scholar
  83. Franzoso G, Bours V, Siebenlist U (1994): unpublished observationGoogle Scholar
  84. Fujita T, Nolan GP, Ghosh S, Baltimore D (1992): Independent modes of transcriptional activation by the p50 and p65 subunits of NF-κB. Genes Dev. 6: 775–787PubMedGoogle Scholar
  85. Fujita T, Nolan GP, Liou H-C, Scott ML, Baltimore D (1993): The candidate protooncogene bcl-3 encodes a transcriptional coactivator that activates through NF- κB p50 homodimers. Genes Dev 7: 1354–1363PubMedGoogle Scholar
  86. Fujita T, Reis LFL, Watanabe N, Kimura Y, Taniguchi T, Vilcek J (1989): Induction of the transcription factor IRF-1 and IFN-β mRNAs by cytokines and activators of second-messenger pathways. Proc Natl Acad Sci USA 86: 9936–9940PubMedGoogle Scholar
  87. Ganchi PA, Sun S-C, Greene WC, Ballard DW (1992): IktB/MAD-3 masks the nuclear localization signal of NF-κB p65 and requires the transactivation domain to inhibit NF-κB p65 DNA binding. Mol Biol Cell 3: 1339–1352PubMedGoogle Scholar
  88. Ganchi PA, Sun SC, Greene WC, Ballard DW (1993): A novel NF-κB complex containing p65 homodimers: implications for transcriptional control at the level of subunit dimerization. Mol Cell Biol 13: 7826–7835PubMedGoogle Scholar
  89. Gay NJ, Ntwasa M (1993): The Drosophila ankyrin repeat protein cactus has a predominantly alpha-helical secondary structure. FEBS Lett 355: 155–160Google Scholar
  90. Geng Y, Zhang B, Lotz M (1993): Protein tyrosine kinase activation is required for lipopolysaccaride induction of cytokines in human blood monocytes. J Immunol 151: 6692–6700PubMedGoogle Scholar
  91. Ghosh S, Baltimore D (1990): Activation in vitro of NF-κB-γ phosphorylation of its inhibitor IκB. Nature 344: 678–682PubMedGoogle Scholar
  92. Ghosh S, Gifford AM, Riviere LR, Tempst P, Nolan GP, Baltimore D (1990): Cloning of the p50 DNA binding subunit of NF-κB: homology to rel and dorsal. Cell 62: 1019–1029PubMedGoogle Scholar
  93. Gilmore TD (1992): Role of rel family genes in normal and malignant lymphoid cell growth. Cancer Surveys 15: 69–87PubMedGoogle Scholar
  94. Gilmore TD, Morin PJ (1993): The IκB proteins: members of a multifunctional family. Trends Genet 9: 427–433PubMedGoogle Scholar
  95. Goldfeld AE, McCaffrey PG, Strominger JL, Rao A (1993): Identification of a novel cyclosporin-sensitive element in the human tumor necrosis factor alpha gene promoter. J Exp Med 178: 1365–1379PubMedGoogle Scholar
  96. Gonzalez-Crespo S, Levine M (1994): Related target enhancers for dorsal and NF-κB signaling pathways. Science 264: 255–258PubMedGoogle Scholar
  97. Govind S, Steward R (1991): Dorsovental pattern formation in Drosophila: signal transduction and nuclear targeting. Trends Gen 7: 119–125Google Scholar
  98. Grassman R, Dengler C, Muller-Fleckenstein I, Fleckenstein B, McGuire K, Dokhelar MC, Sodroski JG, Haseltine WA (1989): Transformation of continuous growth of primary human T lymphocytes by human T-cell leukemia virus type I X-region genes transduced by a Herpesvirus saimiri vector. Proc Natl Acad Sci USA 86: 3351–3355Google Scholar
  99. Grilli M, Jason J-S, Lenardo M J (1993): NF-jcB and rel-participants in a multiform transcriptional regulatory system. Int Rev Cytol 143: 1–62PubMedGoogle Scholar
  100. Grimm S, Baeuerle PA (1993): The inducible transcription factor NF-κB: structurefunction relationship of its protein subunits. Biochem J 290: 297–308PubMedGoogle Scholar
  101. Gross V, Zhang B, Geng Y, Villiger PM, Lotz M (1993): Regulation of interleukin-6 (IL-6) expression: evidence for a tissue-specific role of protein kinase C. J Clin Immunol 13: 310–320PubMedGoogle Scholar
  102. Grove M, Plumb M (1993): C/EBP, NF-κB, and c-Ets family members and transcriptional regulation of the cell specific and inducible macrophage inflammatory protein 1 alpha immediate-early gene. Mol Cell Biol 13: 5276–5289PubMedGoogle Scholar
  103. Grumont RJ, Gerondakis S (1989): Structure of a mammalian c-rel protein deduced from the nucleotide sequence of murine cDNA clones. Oncogene Res 4: 1–8PubMedGoogle Scholar
  104. Grumont RJ, Gerondakis S (1990): Murine c-rel transcription is rapidly induced in T cells and fibroblasts by mitogenic agents and the phorbol ester 12-O-tetradeca-noylphorbol-13-acetate. Cell Growth Differ 1:345–350PubMedGoogle Scholar
  105. Gunter KC, Irving SG, Zipfel PF, Siebenlist U, Kelley K (1989): Cyclosporin A-mediated inhibition of mitogen-induced gene transcription is specific for the mitogenic stimulus and cell type. J Immunol 142: 3286–3291PubMedGoogle Scholar
  106. Hannibal MC, Markovitz DM, Clark N, Nabel GJ (1993): Differential activation of human immunodeficiency virus type 1 and 2 transcription by specific T-cell activation signals. J Virol 67: 5035–5040PubMedGoogle Scholar
  107. Hannink M, Temin HM (1989): Transactivation of gene expression by nuclear and cytoplasmic rel proteins. Mol Cell Biol 9: 4323–4336PubMedGoogle Scholar
  108. Hannink M, Temin HM (1990): Structure and autoregulation of the c-rel promoter. Oncogene 5: 1843–1850PubMedGoogle Scholar
  109. Hansen SK, Baeuerle PA, Blasi F (1994): Purification, reconstitution, and IκB association of the c-Rel-p65 (RelA) complex, a strong activator of transcription. Mol Cell Biol 14: 2593–2603PubMedGoogle Scholar
  110. Hansen SK, Nerlov C, Zabel U, Verde P, Johnsen M, Baeuerle PA, Blasi F (1992): A novel complex between the p65 subunit of NF-κB and c-Rel binds to a DNA element involved in the phorbol ester induction of the human urokinase gene. EMBO J 11:205–213PubMedGoogle Scholar
  111. Harada H, Fujita T, Miyamoto M, Kimura Y, Maruyama M, Furia A, Miyata T, Taniguchi T (1989): Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind to the same regulatory elements of IFN and IFN-inducible genes. Cell 58: 729–739PubMedGoogle Scholar
  112. Harada H, Takahashi E-I, Itoh S, Harada K, Hori T-A (1994): Structure and regulation of the human interferon regulatory factor (IRF-1) and IRF-2 genes: implications for a gene network in the interferon system. Mol Cell Biol 14: 1500–1509PubMedGoogle Scholar
  113. Haskill S, Beg AA, Tompkins SM, Morris JS, Yurochko AD, Sampson-Johannes A, Mondai K, Ralph P, Baldwin AS (1991): Characterization of an immediate-early gene induced in adherent monocytes that encodes IκB-like activity. Cell 65: 1281–1289PubMedGoogle Scholar
  114. Hatada EN, Naumann M, Scheidereit C (1993): Common structural constituents confer IκB activity to NF-/cB p105 and IκB/MAD-3. EMBO J 12: 2781–2788PubMedGoogle Scholar
  115. Hatada EN, Nieters N, Wulczyn FG, Naumann M, Meyer R, Nucifora G, McKeithan TW, Scheidereit C (1992): The ankyrin repeat domains of the NF-κB precursor p005 and the protocogene bcl-3 acts as specific inhibitors of NF-κB DNA binding. Proc Natl Acad Sci USA 89: 2489–2493PubMedGoogle Scholar
  116. Hay RT (1993): Control of nuclear factor-κB DNA-binding activity by inhibitory proteins containing ankyrin repeats. Biochem Soc Trans 21: 926–930PubMedGoogle Scholar
  117. Hayashi T, Ueno Y, Okamoto T (1993): Oxidoreductive regulation of NF-κB. nvolvement of a cellular reducing catalyst thioredoxin. J Biol Chem 268: 11380–11388PubMedGoogle Scholar
  118. Henkel T, Zabel U, vanZee K, Müller JM, Fanning E, Baeuerle PA (1992): Intramolecular masking of the nuclear localization signal and dimerization domain in the precursor for the p50 NF-κB subunit. Cell 68: 1121–1133PubMedGoogle Scholar
  119. Henkel T, Machleidt T, Alkalay I, Kronke M (1993): Rapid proteolysis of IκB-α is necessary for activation of transcription factor NF-κB. Nature68:182–185Google Scholar
  120. Hirai H, Fujisawa J, Suzuki T, Ueda K, Muramatsu M, Tsuboi A, Arai N, Yoshida M (1992): Transcriptional activator tax of HTLV-1 binds to the NF-κB precursor p105. Oncogene 7: 1737–1742PubMedGoogle Scholar
  121. Hiscott J, Marois J, Garoufalis J, D’Addario M (1993): Characterization of a functional NF-κB site in the human interleukin 1 beta promoter: evidence for a positive autoregulatory loop. Mol Cell Biol 13: 6231–6240PubMedGoogle Scholar
  122. Hohmann H-P, Brockhaus M, Baeuerle PA, Remy R (1990a): Expression of the types A and B tumor necrosis factor (TNF) receptors is independently regulated, and both receptors mediate activation of the transcription factor NF-κB. J Biol Chem 265: 22409–22017PubMedGoogle Scholar
  123. Hohmann HP, Remy R, Poschl B, vanLoon AP (1990b): Tumor necrosis factors-α and bind to the same two types of tumor necrosis factor receptors and maximally activate the transcription factor NF-κB at low receptor occupancy and within minutes after receptor binding. J Biol Chem 265: 15183–14188PubMedGoogle Scholar
  124. Hohmann H-P, Remy R, Scheidereit C, vanLoon APGM (1991): Maintenance of NF-κB activity is dependent on protein synthesis and the continuous presence of external stimuli. Mol Cell Biol 11: 259–266PubMedGoogle Scholar
  125. Hoyos B, Ballard DW, Bohnlein E, Siekevitz M, Greene WC (1989): κB-specific DNA binding proteins: role in the regulation of human interleukin-2 gene expression. Science 244: 457–460PubMedGoogle Scholar
  126. Hrdlickova R, Nehyba J, Humphries EH (1994): v-rel induces expression of three avian immunoregulatory surface receptors more efficiently than c-rel. J Vorol 68: 308–319Google Scholar
  127. Hrdlickova R, Nehyba J, Humphries EH (1994b): In vivo evolution of c-rel oncogenic potential. J Virol 68: 2371–2382PubMedGoogle Scholar
  128. Hultmark D (1993): Immune reactions in Drosophila and other insects: a model for innate immunity. Trends Genet 9: 178–193PubMedGoogle Scholar
  129. Hultmark D (1994): Ancient relationships. Nature 367: 116–117PubMedGoogle Scholar
  130. Iademarco MF, McQuillan JJ, Rosen GD, Dean DC (1992): Characterization of the promoter for vascular cell adhesion molecule-1 (VCAM-1). J Biol Chem 267: 16323–16329PubMedGoogle Scholar
  131. Inoue J-I, Kerr LD, Ransone LJ, Bengal E, Hunter T, Verma IM (1991): c-rel activates but v-rel suppresses transcription from κB sites. Proc Natl Acad Sci USA 88: 3715–3719PubMedGoogle Scholar
  132. Inoue JI, Kerr LD, Kakizuka A, Verma IM (1992a): IκB-γ, a 70 kd protein identical to the C-terminal half of p100 NF-κB: a new member of the IκB family. Cell 68: 1109–1120PubMedGoogle Scholar
  133. Inoue J, Kerr LD, Rashid D, Davis N, Böse HR, Verma IM (1992b): Direct association of pp40/IκB-β with rel/NF-κB transcription factors: role of ankyrin repeats in the inhibition of DNA binding activity. Proc Natl Acad Sci USA 89: 4333–4337PubMedGoogle Scholar
  134. Inuzuka M, Ishikawa H, Kumar S, Gelinas C, Ito Y (1994): The viral and cellular Rel oncoproteins induce the differentiation of P19 embryonal carcinoma cells. Oncogene 9: 133–140PubMedGoogle Scholar
  135. Ip YT, Levine M (1992): The role of the dorsal morphogen gradient in Drosophila embryogenesis. Semin Devel Biol 3: 15–23Google Scholar
  136. Ip YT, Kraut R, Levine M, Rushlow C (1991): The dorsal morphogen is a sequence-specific DNA-binding protein that interacts with a long-range repression element in Drosophila. Cell 64: 439–446PubMedGoogle Scholar
  137. Ip YT, Rach M, Engstrom Y, Kadalayil L, Cai H, Gonzalex-Crespo S, Tateri K, Levein M (1993): Dif, a dorsal-related gene that mediates an immune response in Drosophila. Cell 75: 753–763PubMedGoogle Scholar
  138. Ishikawa H, Asano M, Kanda T, Kumar S, Gelinas C, Ito Y (1993): Two novel functions associated with the Rel oncoproteins: DNA replication and cell-specific transcriptional activation. Oncogene 8: 2889–2896PubMedGoogle Scholar
  139. Isoda K, Roth S, Nusslein-Volhard C (1992): The functional domains of the Drosophila morphogen dorsal: evidence from the analysis of mutants. Genes Develop 6: 619–630PubMedGoogle Scholar
  140. Israël A (1992): The rel/NF-κB family of transcription factors: a novel mechanisms to control gene expression (editorial). Pathol Biol 40: 212–214PubMedGoogle Scholar
  141. Iwasaki T, Uehara Y, Graves L, Rachie N, Bomsztyk K (1992): Herbimycin A blocks IL-1-induced NF-κB DNA-binding activity in lymphoid cell lines. Febs Lett 298: 240–244PubMedGoogle Scholar
  142. Jamieson C, McCaffrey PG, Rao A, Sen R (1991): Physiologic activation of T cells via a T-cell receptor induces NF-κB. J Immunol 147: 416–420PubMedGoogle Scholar
  143. Jiang J, Levine M (1993): Binding affinities and cooperative interactions with bHLH activators delimit threshold responses to the dorsal gradient morphogen. Cell 72: 741–752PubMedGoogle Scholar
  144. Johnson DR, Pober JS (1994): HLA class I Heavy-chain gene promoter elements mediating synergy between tumor necrosis factor and interferons. Mol Cell Biol 14: 1322–1332PubMedGoogle Scholar
  145. Joseph CK, Byun HS, Bittman R, Kolesnick RN (1993): Substrate recognition by ceramide-activated protein kinase. Evidence that kinase activity is proline-directed. J Biol Chem 268: 20002–20006PubMedGoogle Scholar
  146. Joshi-Barve SS, Rangnekar VV, Sells SF, Rangnekar VM (1993): Interleukin-1-inducible expression of gro-β via NF-κB activation is dependent upon tyrosine kinase signalling. J Biol Chem 268: 18018–18029PubMedGoogle Scholar
  147. Kaltschmidt B, Baeuerle PA, Kaltschmidt C (1993): Potential involvement of the transcription factor NF-κB in neurological disorders. Mol Aspects Med 14: 171–190PubMedGoogle Scholar
  148. Kamens J, Richardson P, Mosialos G, Brent R, Gilmore TD (1990): Oncogenic transformation by v-Rel requires an amino-terminal activation domain. Mol Cell Biol 10: 2840–2847PubMedGoogle Scholar
  149. Kang SM, Tran AC, Grilli M, Lenardo M J (1992): NF-κB subunit regulation in nontransformed CD4+ T lymphocytes. Science 256: 1452–1456PubMedGoogle Scholar
  150. Kanno T, Brown K, Franzoso G, Siebenlist U (1994a): Kinetic analysis of Human T-cell Leukemia Virus type I Tax-mediated activation of NF-κB. Mol Cell Biol 14: in pressGoogle Scholar
  151. Kanno T, Franzoso G, Siebenlist U (1994b): HTLV-I Tax Mediated activation of NF-κB from novel p100 (NF-κB2)-inhibited cytoplasmic reservoirs. Proc Natl Acad Sci USA 91: in pressGoogle Scholar
  152. Kaszubska W, vanHuijsduijnen RH, Ghersa P, DeRaemy-Schenk AM (1993): Cyclic AMP-independent ATF family members interact with NF-κB and function in the activation of the E-selection promoter in response to cytokines. Mol Cell Biol 13: 7180–7190PubMedGoogle Scholar
  153. Kelly K, Davis P, Mitsuya H, Irving S, Wright J, Grassman R, Fleckenstein B, Wano Y, Greene W, Siebenlist U (1992): A high proportion of early response genes are constitutively activated in T cells by HTLV-1. Oncogene 7: 1463–1470PubMedGoogle Scholar
  154. Kerr LD, Duckett CS, Wamsley P, Zhang Q, Chiao P, Nabel G, McKeithan TW, Baeuerle PA, Verma I (1992): The protooncogene BCL-3 encodes an IκB protein. Genes Dev 6: 2352–2363PubMedGoogle Scholar
  155. Kerr LD, Inoue J-I, Davis N, Link E, Baeuerle PA, Bose HR, Verma IM (1991): The Relassociated pp40 protein prevents DNA binding of Rel and NF-κB: relationship with IκB-β and regulation by phosphorylation. Genes Development 5: 1464–1476PubMedGoogle Scholar
  156. Kerr LD, Ransone LJ, Wamsley P, Schmitt MJ, Boyer TG, Zhou Q, Berk AJ, Verma IM (1993): Association between proto-oncoprotein Rel and TATA-binding protein mediates transcriptional activation by NF-κB. Nature 365: 412–419PubMedGoogle Scholar
  157. Kessler DJ, Duyao M, Spicer DB, Sonenshein GE (1992): NF-κB-like factors mediate interleukin 1 induction of c-myc gene transcription in fibroblasts. J Exp Med 176: 787–792PubMedGoogle Scholar
  158. Kieran M, Blank V, Logeat F, Vandekerchove J, Lottspeich F, LeBail O, Urban MB, Kourilsky P, Baeuerle PA, Israel A (1990): The DNA binding subunit of NF-κB is identical to factor KBF1 and homologous to the rel oncogene product. Cell 62: 1007–1018PubMedGoogle Scholar
  159. Kitajima I, Shinohara T, Bilakovics J, Brown DA (1993): Ablation of transplanted HTLV-I tax-transformed tumors in mice by antisense inhibition of NF-κB. Science 259: 1523PubMedGoogle Scholar
  160. Klug CA, Gerety SJ, Shah PC, Chen Y-Y, Rice NR, Rosenbern, Singh H (1994): The v-abl tyrosine kinase negatively regulates NF-κB/Rel factors and blocks kappa gene transcription in pre-B lymphocytes. Genes Dev 8:678–687PubMedGoogle Scholar
  161. Koong AC, Chen EY, Giaccia AJ (1994): Hypoxia causes the activation of nuclear factor kappa B through the phosphorylation of I kappa B alpha on tyrosine residues. Cancer Res 54: 1425–1430PubMedGoogle Scholar
  162. Kowalik TF, Wing B, Haskill JS, Azizkhan JC, Baldwin AS, Huang E-S (1993): Multiple mechanisms are implicated in the regulation of NF-κB activity during human cytomegalovirus infection. Proc Natl Acad Sci USA 90: 1107–1111PubMedGoogle Scholar
  163. Kralova J, Schatzle JD, Bargmann W, Bose HR (1994): Transformation of avian fibroblasts overexpressing the c-rel proto-oncogene and a variant of c-rel lacking 40 C-terminal amino acids. J Virol 68: 2073–2083PubMedGoogle Scholar
  164. Kretzschmar M, Meisterernst M, Scheidereit C, Li G, Roeder RG (1992): Transcriptional regulation of the HIV-1 promoter by NF-κB in vitro. Genes Dev. 6: 761–774PubMedGoogle Scholar
  165. Krikos A, Laherty CD, Dixit VM (1992): Transcriptional activation of the tumor necrosis factor alpha-inducible zinc finger protein, A20, is mediated by kappa B elements. J Biol Chem 267: 17971–17976PubMedGoogle Scholar
  166. Kuang AA, Novak KD, Kang SM, Bruhn K, Lenardo MJ (1993): Interaction between NF-κB- and serum response factor binding elements activates an interleukin-2 receptor alpha-chain enhancer specifically in T lymphocytes. Mol Cell Biol 13: 2536–2545PubMedGoogle Scholar
  167. Kumar S, Gelinas C (1993): IκB α-mediated inhibition of v-Rel DNA binding requires direct interaction with the RXXRXRXXC Rel/κB DNA-binding motif. Proc Natl Acad Sci USA 90: 8962–8966PubMedGoogle Scholar
  168. Kumar S, Rabson AB, Gelinas C (1992): The RxxRxRxxC motif conserved in all Rel/κB proteins is essential for the DNA-binding activity and redox regulation of the v-Rel oncoprotein. Mol Cell Biol 12: 3094–3106PubMedGoogle Scholar
  169. Kunsch C, Rosen CA (1993): NF-κB subunit-specific regulation of the interleukin-8 promoter. Mol Cell Biol 13: 6137–6146PubMedGoogle Scholar
  170. Kunsch C, Ruben SM, Rosen CA (1992): Selection of optimal κB Rel DNA-binding motifs: interaction of both subunits of NF-κB with DNA is required for transcriptional activation. Mol Cell Biol 12: 4412–4421PubMedGoogle Scholar
  171. Lalmanach-Girard AC, Chiles TC, Parker DC, Rothstein TL (1993): T cell-dependent induction of NF-κB in B cells. J Exp Med 177: 1215–1219PubMedGoogle Scholar
  172. La Rosa FA, Pierce JW, Sonenshein GE (1994): Differential regulation of the c-myc oncogene promoter by the NF-κB rel family of transcription factors. Mol Cell Biol 14: 1039–1044PubMedGoogle Scholar
  173. LeBail O, Schmidt-Ullrich R, Israel A (1993): Promoter analysis of the gene encoding the IκB-α/M AD3 inhibitor of NF-κB: positive regulation by members of the rel/ NF-κB family. EMBO J 12: 5043–5049Google Scholar
  174. LeClair KP, Blanar MA, Sharp PA (1992): The p50 subunit of NF-κB associates with the NF-IL6 transcription factor. Proc Natl Acad Sci USA 89: 8145–8149PubMedGoogle Scholar
  175. Lee-Huang S, Lin JJ, Kung HF, Huang PL (1993): The human erythropoietin-encoding gene contains a CAAT box, TATA boxes and other transcriptional regulatory elements in its 5’ flanking region. Gene 128: 227–236PubMedGoogle Scholar
  176. Leiden JM, Wang CY, Petryniak B, Markovitz DM (1992): A novel Ets- related transcription factor, Elf-1, binds to human immunodeficiency virus type 2 regulatory elements that are required for inducible trans activation in T cells. J Virol 66: 5890–5897PubMedGoogle Scholar
  177. Lenardo M, Siebenlist U (1994): Bcl-3-mediated nuclear regulation of the NF-κB trans-activating factor. Immunol Today 15: 145–146PubMedGoogle Scholar
  178. Lernbecher T, Muller U, Wirth T (1993): Distinct NF-κB/Rel transcription factors are responsible for tissue-specific and inducible gene activation. Nature 365: 767–770PubMedGoogle Scholar
  179. Li S, Sedivy JM (1993): Raf-1 protein kinase activates the NF-κB transcription factor by dissociating the cytoplasmic NF-κB-IκB complex. Proc Natl Acad Sci USA 90: 9247–9251PubMedGoogle Scholar
  180. Liao F, Andalibi F, deBeer FC, Fogelman AM, Lusis AJ (1993): Genetic control of inflammatory gene induction and NF-κB-like transcription factor activation in response to an atherogenic diet in mice. J Clin Invest 91: 2572–2479PubMedGoogle Scholar
  181. Lichtenstein M, Keini G, Cedar H, Bergman Y (1994): B cell-specific demethylation: a novel role for the intronic kappa chain enhancer sequence. Cell 76: 913–923PubMedGoogle Scholar
  182. Lin YC, Brown K, Siebenlist U (1994): unpublished observationsGoogle Scholar
  183. Lindholm P, Reid RL, Brady JN (1992): Extracellular Tax-1 protein stimulates tumor necrosis factor-β and immunoglobulin k light chain expression in lymphoid cells.J Virol 66: 1294–1302PubMedGoogle Scholar
  184. Link E, Kerr LD, Schreck R, Zabel U, Verma I, Baeuerle PA (1992): Purified IκB is inactivated upon dephosphorylation. J Biol Chem 267: 239–246PubMedGoogle Scholar
  185. Liou HC, Baltimore D (1993): Regulation of the NF-κB/rel transcription factor and IκB inhibitor system. Curr Opin Cell Biol 5: 477–487PubMedGoogle Scholar
  186. Liou HC, Nolan GP, Ghosh S, Fujita T, Baltimore D (1992): The NF-κB p50 precursor, p105, contains an internal IκB-like inhibitor that preferentially inhibits p50. EMBO J 11: 3003–3009PubMedGoogle Scholar
  187. Liu J, Sodeoka M, Lane WS, Verdine GL (1994): Evidence for a non-alpha-helical DNA-binding motif in the Rel homology region. Proc Natl Acad Sci USA 91: 908–912PubMedGoogle Scholar
  188. Logeat F, Israël N, Ten R, Blank V, LeBail, Kourilsky P, Israel A (1991): Inhibition of transcription factors belonging to the rel/NF-κB family by a transdominant negative mutant. EMBO J 10: 1827–1832PubMedGoogle Scholar
  189. Lowenstein CJ, Alley EW, Raval P, Snowman AM, Snyder SH, Russell SW, Murphy WJ (1993): Macrophage nitric oxide synthase gene: two upstream regions mediate induction by interferon gamma and lipopolysaccharide. Proc Natl Acad Sci USA 90: 9730–9734PubMedGoogle Scholar
  190. Lu D, Thompson JD, Gorski GK, Rice NR, Mayer MG, Yunis JJ (1991): Alterations at the rel locus in human lymphoma. Oncogene 6: 1235–1241PubMedGoogle Scholar
  191. Mathias S, Dressler KA, Kolesnick RN (1991): Characterization of a ceramide-activated protein kinase: stimulation by tumor necrosis factor a. J Biol Chem 88: 10009–10013Google Scholar
  192. Mathias S, Younes A, Kan CC, Orlow I, Joseph C, Kolesnick RN (1993): Activation of the spingomyelin signaling pathway in intact EL4 cells and in a cell-free system by IL-1β. Science 259: 519–522PubMedGoogle Scholar
  193. Matsusaka T, Fujikawa K, Nishio Y, Mukaida N (1993): Transcription factors NF-IL6 and NF-κB synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8. Proc Natl Acad Sci USA 90: 10193–10197PubMedGoogle Scholar
  194. Matthews JR, Kaszubska W, Turcatti G, Wells TN, Hay RT (1993a): Role of cysteine 62 in DNA recognition by the P50 subunit of NF-κB. Nucleic Acids Res 21: 1727–1734PubMedGoogle Scholar
  195. Matthews JR, Wakasugi N, Virelizier J-L, Yodoi J, Hay RT (1992): Thioredoxin regulates the DNA binding activity of NF-κB by reduction of a disulfide bond involving cysteine 62. Nucl Acids Res 30: 3821–3830Google Scholar
  196. Matthews JR, Watson E, Buckley S, Hay RT (1993b): Interaction of the C-terminal region of p105 with the nuclear localisation signal of p50 is required for inhibition of NF-κB DNA binding activity. Nucleic Acids Res 21: 4516–4523PubMedGoogle Scholar
  197. McDonnell PC, Kumar S, Rabson AB, Gelinas C (1992): Transcriptional activity of rel family proteins. Oncogene 7: 163–170PubMedGoogle Scholar
  198. Meichle A, Schutze S, Hensel G, Brunsing D, Kronke M (1990): Protein kinase C-independent activation of nuclear factor κB by tumor necrosis factor. J Biol Chem 265: 8339–8343PubMedGoogle Scholar
  199. Mellits KH, Hay RT, Goodburn S (1993): Proteolytic degradation of MAD3 (IκB alpha) and enhanced processing of the NF-κB precursor pi05 are obligatory steps in the activation of NF-κB. Nucleic Acids Res 21: 5059–5066PubMedGoogle Scholar
  200. Menon SD, Qin S, Guy GR, Tan YH (1993): Differential induction of nuclear NF-κB by protein phosphatase inhibitors in primary and transformed human cells. J Biol Chem 268: 26805–26812PubMedGoogle Scholar
  201. Mercurio F, Didonato J, Rosette C, Karin M (1992): Molecular cloning and characterization of a novel Rel/NF-κB family member displaying structural and functional homology to NF-κB p50-pl05. DNA Cell Biol 11: 523–537PubMedGoogle Scholar
  202. Mercurio F, Didonato JA, Rossette C, Karin M (1993): p105 and p98 precursor proteins play an active role in NF-κB-mediated signal transduction. Genes Dev. 7: 705–718PubMedGoogle Scholar
  203. Messer G, Weiss EH, Baeuerle PA (1990): Tumor necrosis factor beta (TNF-β) induces binding of the NF-κB transcription factor to a high-affinity κB element in the TNF-β promoter. Cytokine 2: 389–397PubMedGoogle Scholar
  204. Meyer R, Hatada EN, Hohmann HP, Haiker M, Bartsch C, Rothlisberger U, Lahm HW, Schlaeger EJ, vanLoon APGM, Schiedereit C (1991): Cloning of the DNA-binding subunit of human nuclear factor kB: the level of its mRNA is strongly regulated by phorbol ester or tumor necrosis factor a. Proc Natl Acad Sci USA 88: 966–970PubMedGoogle Scholar
  205. Meyer M, Schreck R, Baeuerle PA (1993a): H2O2 and antioxidants have opposite effects on activation of NF-/cB and AP-1 in intact cells: Ap-1 as secondary antioxidant-responsive factor. EMBO J 12: 2005–2015PubMedGoogle Scholar
  206. Meyer M, Schreck R, Muller J, Baeuerle PA (1993b): Redox control of gene expression by eukaryotic transcription factors NF-κB, AP-1 and SRF/TCF. In: Oxidative Stress, Cell Activation and Viral Infection, Packer L, Pasquier C, eds. Basel: Birkhauser VerlagGoogle Scholar
  207. Michaely P, Bennett V (1992): The ANK repeat: a ubiquitous motif involved in macromolecular recognition. Trends Cell Biol 2: 127–129PubMedGoogle Scholar
  208. Miyamoto S, Chiao PJ, Verma IM (1994): Enhanced IκBα degradation is responsible for constitutive NF-κB activity in mature murine B-cell lines. Mol Cell Biol 14: 3276–3282PubMedGoogle Scholar
  209. Miyamoto M, Fujita T, Kimura Y, Maruyama M, Harada H, Sudo Y, Miyata T, Taniguchi T (1988): Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-β gene regulatory elements. Cell 54: 903–913PubMedGoogle Scholar
  210. Molitor JA, Walker WH, Doerre S, Ballard DW, Greene WC (1990): NF-κB: a family of inducible and differentially expressed enhancer-binding proteins in human T cells. Proc Natl Acad Sci USA 87: 10028–10032PubMedGoogle Scholar
  211. Moore PA, Ruben SM, Rosen CA (1993): Conservation of transcriptional activation functions of the NF-κB p50 and p65 subunits in mammalian cells and Saccharomyces cerevisiae. Mol Cell Biol 13: 1666–1674PubMedGoogle Scholar
  212. Morrison LE, Boehmelt G, Beug H, Enrietto PJ (1992): Expression of v-rel by a replication-competent virus in chicken embryo fibroblasts. Oncogene 6: 1657–1666Google Scholar
  213. Muller JM, Ziegler-Heitbrock JHW, Baeuerle PA (1993): Nuclear factor κB, a mediator of lipopolysaccharide effects. Immunobiol 187: 233–256Google Scholar
  214. Muroi M, Suzuki T (1993): Role of protein kinase A in LPS-induced activation of NF-κB proteins of a mouse macrophage-like cell line, J774. Cellular Signaling 5: 289–298Google Scholar
  215. Nabel G, Baltimore D (1987): An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature 326: 711–713PubMedGoogle Scholar
  216. Nakayama K, Shimizu H, Mitomo K, Watanabe T (1992): A lymphoid cell-specific nuclear factor containing c-Rel-like proteins preferentially interacts with inter-leukin-6 κB-related motifs whose activities are repressed in lymphoid cells. Mol Cell Biol 12: 1736–1746PubMedGoogle Scholar
  217. Narayanan R, Higgins KA, Perez JR, Coleman TA, Rosen CA (1993): Evidence for differential functions of the p50 and p65 subunits of NF-κB with a cell adhesion model. Mol Cell Biol 13: 3802–3810PubMedGoogle Scholar
  218. Naumann M, Wulczyn FG, Scheidereit C (1993): The NF-κB precursor pl05 and the proto-oncogene product Bcl-3 are IκB molecules and control nuclear translocation of NF-κB. EMBO J 12: 213–222PubMedGoogle Scholar
  219. Nehyba J, Hrdlickova R, Humphries EH (1994): Evolution of the oncogenic potential of v-rel: rel-induced expression of immunoregulatory receptors correlates with tumor development and in vitro transformation. J Virol 68: 2039–2050PubMedGoogle Scholar
  220. Neiman PE, Thomas SJ, Loring G (1991): Induction of apoptosis during normal and neoplastic B-cell development in the bursa of Fabricius. Proc Natl Acad Sci USA 88: 5857–5861PubMedGoogle Scholar
  221. Neish AS, Williams AJ, Palmer H J, Whitley MZ, Collins T (1992): Functional analysis of the human vascular cell adhesion molecule 1 promoter. J Exp Med 176: 1583–1593PubMedGoogle Scholar
  222. Nerenberg M, Hinrichs SH, Reynolds RK, Khoury G, Jay G (1987): The tat gene of human T-lymphotropic virus type 1 induces messenchymal tumors in transgenic mice. Science 237: 1324–1329PubMedGoogle Scholar
  223. Neri A, Chang CC, Lombardi L, Salina M, Corradini P, Maiolo AT, Chaganti RSK, Dalla-Favera R (1991): B cell lymphoma-associated chromosomal translocation involves candidate oncogene lyt-10, homologous to NF-κB p50. Cell 67: 1075–1087PubMedGoogle Scholar
  224. Niederman TMJ, Garcia JV, Hastings WR, Luria S, Ratner L (1992): Human immunodeficiency virus type 1 nef protein inhibits NF-κB induction in human T cells. J Virol 66: 6213–6219PubMedGoogle Scholar
  225. Nielsch U, Zimmer SG, Babiss LE (1991): Changes in NF-kappa B and ISGF3 DNA binding activities are responsible for differences in MHC and beta-IFN gene expression in Ad5-versus Adl2-transformed cells. Embo J 10: 4169–4175PubMedGoogle Scholar
  226. Nolan GP, Baltimore D (1992): The inhibitory ankyrin and activator Rel proteins. Curr Opin Genet Dev 2: 211–220PubMedGoogle Scholar
  227. Nolan GP, Fujita T, Bhatia K, Huppi K, Liou H-C, Scott ML, Baltimore D (1993): The bcl-3 proto-oncogene encodes a nuclear IκB-like molecule that preferentially interacts with NF-κB p50 in a phosphorylation-dependent manner. Mol Cell Biol 13: 3557–3566PubMedGoogle Scholar
  228. Nolan GP, Ghosh S, Liou H-C, Tempst P, Baltimore D (1991): DNA binding and IκB inhibition of the cloned p65 subunit of NF-κB, a rel-related polypeptide. Cell 64: 961–969PubMedGoogle Scholar
  229. Norris JL, Manley JL (1992): Selective nuclear transport of the Dorsophila morphogene dorsal can be established by a signaling pathway involving the transmembrane protein Toll and protein kinase A. Genes Devel 6: 1654–1667PubMedGoogle Scholar
  230. Ohmori Y, Hamilton TA (1993): Cooperative interaction between interferon (IFN) stimulus response element and κB sequence motifs controls IFN-γ- and lipopo-lysaccharide-stimulated transcription from the murine IP-10 promoter. J Biol Chem 268: 6677–6688PubMedGoogle Scholar
  231. Ohno H, Takimoto G, McKeithan TW (1990): The candidate proto-oncogene bcl-3 is related to genes implicated in cell lineage determination and cell cycle control. Cell 60: 991–997PubMedGoogle Scholar
  232. Olashaw NE, Kowalik TF, Huang ES, Pledger WJ (1992): Induction of NF-κB-hke activity by platelet-derived growth factor in mouse fibroblasts. Mol Biol Cell 3: 1131–1139PubMedGoogle Scholar
  233. Osborn L, Kunkel S, Nabel GJ (1989): TNF-α and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the NF-κB. Proc Natl Acad Sci USA 86: 2336–2340PubMedGoogle Scholar
  234. Pantaleo G, Graziosi C, Demarest JF, Butini L (1993a): HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature 362: 355–358PubMedGoogle Scholar
  235. Pantaleo G, Graziosi C, Fauci AS (1993b): New concepts in the immunopathogenesis of human immunodeficiency virus infection. N Engl J Med 328: 327–335PubMedGoogle Scholar
  236. Parhami F, Fang ZT, Fogelman AM, Andalibi A (1993): Minimally modified low density lipoprotein-induced inflammatory responses in endothelial cells are mediated by cyclic adenosine monophosphate. J Clin Invest 92: 471–478PubMedGoogle Scholar
  237. Paya CV, Ten RM, Bessia C, Alcami J, Hay RT, Virelizier J-L (1992): NF-κB-dependent induction of the NF-κB p50 subunit gene promoter underlies self-perpetuation of human immunodeficiency virus transcription in monocytic cells. Proc Natl Acad Sci USA 89: 7826–7830PubMedGoogle Scholar
  238. Perkins ND, Edwards NL, Duckett CS, Agranoff AB (1993): A cooperative interaction between NF-κB and Spl is required for HIV-1 enhancer activation. EMBO J 12: 3551–3558PubMedGoogle Scholar
  239. Perkins ND, Schmid RM, Duckett CS, Leung K, Rice NR, Nabel GJ (1992): Distinct combinations of NF-κB subunits determine the specificity of transcriptional activation. Proc Natl Acad Sci USA 89: 1529–1533PubMedGoogle Scholar
  240. Pierce JW, Lenardo M, Baltimore D (1988): An oligonucleotide that binds nuclear factor NF-κB acts as a lymphoid-specific and inducible enhancer element. Proc Natl Acad Sci USA 85: 1482–1486PubMedGoogle Scholar
  241. Plaksin D, Baeuerle P, Eisenbach L (1993): KBF-1 (p50 NF-κB homodimer) acts as a repressor of H-2Kb gene expression in metastatic tumor cells.J Exp Med 177: 1651–1662PubMedGoogle Scholar
  242. Ranganathan PN, Khalili K (1993): The transcriptional enhancer element, κB, regulates promoter activity of the human neurotropic virus, JCV, in cells derived from the CNS. Nucleic Acids Res 21: 1959–1964PubMedGoogle Scholar
  243. Ray KP, Kennard N (1993): Interleukin-1 induces a nuclear form of transcription factor NF kappa B in human lung epithelial cells. Agents Actions 38: C61–3PubMedGoogle Scholar
  244. Ray A, Prefontaine KE (1994): Physical association and functional antagonism between the p65 subunit of transcription factor NF-κB and the glucocorticoid receptor. Pro Natl Acad Sci USA 91: 752–756Google Scholar
  245. Read MA, Whitley MZ, Williams AJ, Collins T (1994): NF-κB and IκB-α: an inducible regulatory system in endothelial activation. J Exp Med 179: 503–412PubMedGoogle Scholar
  246. Reis LFL, Harada H, Wolchok JD, Taniguchi T, Vilcek J (1992): Critical role of a common transcription factor, IRF-1, in the regulation of IFN-β and IFN- inducible genes. EMBO 7 11: 185–193Google Scholar
  247. Rice NR, Ernst MK (1993): In vivo control of NF-κB activation by IκB-α. EMBO J 12: 4685–4695PubMedGoogle Scholar
  248. Rice NR, Gilden RV (1988): The rel oncogene. In: The Oncogene Handbook, Reddy EP, Skalka AM, Curran T, eds. Amsterdam: Elsevier SciGoogle Scholar
  249. Rice NR, MacKichan ML, Israel A (1992): The precursor of NF-κB p50 has IκB-like functions. Cell 71: 243–253PubMedGoogle Scholar
  250. Richardson PM, Gilmore TD (1991): vRel is an inactive member of the Rel family of transcriptional activating proteins. J Virol 65: 3122–3230PubMedGoogle Scholar
  251. Riviere Y, Blank V, Kourilsky P, Israel A (1991): Processing of the precursor of NF-κB by the HIV-1 protease during acute infection. Nature 350: 622–625Google Scholar
  252. Ron D, Brasier AR, Habener JF (1990): Transcriptional regulation of hepatic angiotensinogen gene expression by the acute-phase response. Mol Cell Endocrinol 74: C97–104PubMedGoogle Scholar
  253. Ron D, Brasier AR, Habener JF (1991): A new family of large nuclear proteins that recognize nuclear factor kappa B-binding sites through a zinc finger motif. Mol Cell Biol 11: 2887–2895PubMedGoogle Scholar
  254. Ross I, Buckler-White AJ, Rabson AB, Ingland G, Martin MA (1991): Contribution of NF-κB and SP1 binding motifs to the replicative capacity of human immunodeficiency virus type 1: distinct patterns of viral growth are determined by T cell types.J Virol 65: 4350–4358PubMedGoogle Scholar
  255. Roulston A, Beauparlant P, Rice N, Hiscott J (1993): Chronic human immunodeficiency virus type 1 infection stimulates distinct NF-κB B/rel DNA binding activities in myelomonoblastic cells. J Virol 67: 5235–5246PubMedGoogle Scholar
  256. Roulston A, D’Addario M, Boulerice F, Caplan S, Wainberg MA, Hiscott J (1992): Induction of monocytic differentiation and NF-jcB-like activities by human immunodeficiency virus 1 infection of myelomonoblastic cells. J Exp Med 175: 751–763PubMedGoogle Scholar
  257. Ruben SM, Dillon PJ, Schreck R, Henkel T, Chen CH, Maher M, Baeuerle PA, Rosen CA (1991): Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-κB. Science 251: 1490–1493PubMedGoogle Scholar
  258. Ruben SM, Klement JF, Coleman TA, Maher M, Chen CH, Rosen CA (1992): I-Rel: a novel rel-related protein that inhibits NF-κB transcriptional activity. Genes Dev. 6: 745–760PubMedGoogle Scholar
  259. Ryseck RP, Bull P, Takamiya M, Bours V, Siebenlist U, Dobrzanski P, Bravo R (1992): RelB, a new rel family transcription activator that can interact with p50-NF-κB. Mol Cell Biol 12: 674–684PubMedGoogle Scholar
  260. Ryter SW, Gomer CJ (1993): Nuclear factor κB binding activity in mouse L1210 cells following photofrin II-mediated photosensitization. Photochem Photobiol 58: 753–756PubMedGoogle Scholar
  261. Saklatvala J, Rawlinson LM, Marshall CJ, Kracht M (1993): Interleukin-1 and tumour necrosis factor activate the mitogen activated protein (MAP) kinase kinase in cultured cells. FEBS Lett 334: 189–192PubMedGoogle Scholar
  262. Sambucetti LC, Cherrington JM, Wilkinson GWG, Mocarski ES (1989): NF-κB activation of the cytomegalovirus enhancer is mediated by a viral transactivator and by T cell stimulation. EMBO J 8: 4251–4258PubMedGoogle Scholar
  263. Sarkar S, Gilmore TD (1993): Transformation by the vRel oncoprotein requires sequences carboxy-terminal to the Rel homology domain. Oncogene 8: 2245–2252PubMedGoogle Scholar
  264. Scheinman RI, Beg AA, Baldwin AS (1993): NF-κB p100 (lyt-10) is a component of H2TF1 and can function as an IB-like molecule. Mol Cell Biol 13: 6089–6101PubMedGoogle Scholar
  265. Schieven GL, Kirihara JM, Myers DE, Ledbetter JA, Uckun FM (1993): Reactive oxygen intermediates activate NF-κB in a tyrosine-kinase dependent mechanisms and in combination with vanadate activate the p56 lck and p59 fyn tyrosine kinase in human lymphocytes. Blood 82: 1212–1220PubMedGoogle Scholar
  266. Schmidt A, Hennighausen L, Siebenlist U (1990): Inducible nuclear factor binding to the kappa B elements of the human immunodeficiency virus enhancer in T cells can be blocked by cyclosporin A in a signal-dependent manner. J Virol 64:4037–4041PubMedGoogle Scholar
  267. Schmitz ML, Baeuerle PA (1991): The p65 is responsible for the strong transcription activation potential of NF-κB. EMBO J 10: 3805–3817PubMedGoogle Scholar
  268. Schmitz ML, Henkel T, Baeuerle PA (1991): Proteins controlling the nuclear uptake of the NF-κB, rel and dorsal. Trends Cell Biol 1: 130–137PubMedGoogle Scholar
  269. Schreck R, Albermann K, Baeuerle PA (1992a): NF-κB: an oxidative stress-responsive transcription factor of eukaryotic cells (a review). Free Rad Res Comms 17: 221–237Google Scholar
  270. Schreck R, Bevec D, Dukor B, Baeuerle PA, Chedid L, Bahr GM (1992b): Selection of a muramyl peptide based on its lack of activation of nuclear factor-κB as a potential adjuvant for AIDS vaccines. Clin Exp Immunol 90: 188–193PubMedGoogle Scholar
  271. Schreck R, Grassman R, Fleckenstein B, Baeuerle PA (1992c): Antioxidants selectively suppress activation of NF-κB by human T-cell leukemia virus type I tax protein.J Virol 66: 6288–6293PubMedGoogle Scholar
  272. Schreck R, Meier B, Maennel DN, Droge W, Baeuerle A (1992d): Dithiocarbamates as potent inhibitors of nuclear factor κB activation in intact cells. J Exp Med 175: 1181–1194PubMedGoogle Scholar
  273. Schreck R, Rieber P, Baeuerle PA (1991): Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-κB transcription factor and HIV-1. EMBO J 10: 2247–2258PubMedGoogle Scholar
  274. Schreck R, Zorbas H, Winnacker EL, Baeuerle PA (1990): The NF-κB transcription factor induces DNA binding which is modulated by its 65-kD subunit. Nucl Acids Res 18:6497–6502PubMedGoogle Scholar
  275. Schulze-Osthof T K, Bakker AC, Vanhaesebroeck B, Beyaert R, Jacob WA, Fiers W (1992): Cytotoxic activity of tumor necrosis factor is mediated by early damage to mitochondrial functions _ evidence for the involvement of mitochondrial adical generation.J Biol Chem 267: 5317–5322Google Scholar
  276. Schulze-Osthoff K, Beyaert R, Vandervoorde V, Haegeman G, Fiers W (1993): Depletion of the mitochondrial electron transport abbrogates the cytotoxic and gene induction effects of toxic and gene induction effects of TNF. EMBO J 12: 3095–3104PubMedGoogle Scholar
  277. Schutze S, Pothoff K, Machleidt T, Bercovic D, Wiegmann K, Kronke M (1992): TNF activates NF-κB by phosphatidylcholine-specific phospholipase C-induced “acidic” sphingomyelin breakdown. Cell 71: 765–776PubMedGoogle Scholar
  278. Scott ML, Fujita T, Liou HC, Nolan GP, Baltimore D (1993): The p65 subunit of NF-κB regulates IκB by two distinct mechanisms. Genes Dev 7: 1266–1276PubMedGoogle Scholar
  279. Segars JH, Nagata T, Bours V, Medin IA, Franzoso G, Blanco JCG, Drew PD, Becker KG, An J, Tang T, Stephany DA, Neel B, Siebenlist U, Ozato K (1993): Retinoic acid induction of major histocompatibility class complex I genes in NTera-2 embryonal carcinoma cells involves induction of NF-κB (p50-p-65) and retinoic acid beta-retinoid x receptor beta heterodimers. Mol Cell Biol 13: 6157–6169PubMedGoogle Scholar
  280. Sen R, Baltimore D (1986a): Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell 46: 705–716PubMedGoogle Scholar
  281. Sen R, Baltimore D (1986b): Inducibility of κ immunoglobulin enhancer-binding protein NF-κB by a posttranslational mechanism. Cell 47: 921–928PubMedGoogle Scholar
  282. Shattuck RL, Wood LD, Jaffe GJ, Richmond A (1994): MGSA/GRO transcription is differentially regulated in normal retinal pigment epithelial and melanoma cells. Mol Cell Biol 14: 191–802Google Scholar
  283. Shelton CA, Wasserman SA (1993): pelle encodes a protein kinase required to establish dorsoventral polarity in the Drosophila embryo. Cell 72: 515–525PubMedGoogle Scholar
  284. Shirakawa F, Mizel SB (1989): In vitro activation and nuclear translocation of NF-κB catalyzed by cyclic AMP-dependent protein kinase and protein kinase C. Mol Cell Biol 9: 2424–2430PubMedGoogle Scholar
  285. Shu HB, Agranoff AB, Nabel EG, Leung K (1993): Differential regulation of vascular cell adhesion molecule 1 gene expression by specific NF-κB subunits in endothelial and epithelial cells. Mol Cell Biol 13: 6283–6289PubMedGoogle Scholar
  286. Smith MR, Greene WC (1991): Molecular biology of type I human T-cell leukemia virus (HTLV-I) and adult T-cell leukemia. J Clin Invest 87: 761–766PubMedGoogle Scholar
  287. Sokoloski JA, Sartorelli AC, Rosen CA, Narayanan R (1993): Antisense oligonucleotides to the p65 subunit of NF-κB block CD11b expression and alter adhesion properties of differentiated HL-60 granulocytes. Blood 82: 625–632PubMedGoogle Scholar
  288. St. Johnston D, Nusslein-Volhard C (1992): The origin of pattern and polarity in the Drosophila embryo. Cell 68: 201–219PubMedGoogle Scholar
  289. Staudt LM, Lenardo MJ (1991): Immunoglobulin gene transcription. Annu Rev Immunol 9: 373–398PubMedGoogle Scholar
  290. Stein B, Baldwin AS (1993): Distinct mechanisms for regulation of the interleukin-8 gene involve synergism and cooperativity between C/EBP and NF-κB. Mol Cell Biol 13: 7191–7198PubMedGoogle Scholar
  291. Stein B, Baldwin AS, Ballard DW, Greene WC, Angel P, Herrlich P (1993a): Cross-coupling of the NF-κB p65 and Fos/Jun transcription factors produces potentiated biological function. EMBO J 12: 3879–3891PubMedGoogle Scholar
  292. Stein B, Cogswell PC, Baldwin AS (1993b): Functional and physical associations between NF-κB and C/EBP family members: a rel domain b-ZIP interaction. Mol Cell Biol 13: 3964–3974PubMedGoogle Scholar
  293. Stephens RM, Rice NR, Hiebsch RR, Bose HR, Gilden RV (1983): Nucleotide sequence of v-rel: the oncogene of the reticuloendotheliosis virus. Proc Natl Acad Sci USA 80: 6229–6232PubMedGoogle Scholar
  294. Steward R (1987): Dorsal, an embryonic polarity gene in Drosophila is homologous to the vertebrate proto-oncogene, c-rel. Science 238: 692–694PubMedGoogle Scholar
  295. Stylianou E, O’Neill LA, Rawlinson L, Edbrooke MR (1992): Interleukin 1 induces NF-κB through its type I but not its type II receptor in lymphocytes.J Biol Chem 267: 15836–15841PubMedGoogle Scholar
  296. Sun S-C, Ganchi PA, Ballard DW, Greene WC (1993): NF-κB controls expression of inhibitor IκBa: evidence for an inducible autoregulatory pathway. Science 259: 1912–1915PubMedGoogle Scholar
  297. Sun S-C, Ganchi PA, Beraud C, Ballard DW, Greene WC (1994): Autoregulation of the NF-κB transactivator RelA (p65) by multiple cytoplasmic inhibitors containing ankyrin motifs. Proc Natl Acad Sci USA 91: 1346–1350PubMedGoogle Scholar
  298. Suzuki T, Hirai H, Fujisawa J, Fujita T, Yoshida M (1993): A trans-activator Tax of human T-cell leukemia virus type 1 binds to NF-κB p50 and serum response factor (SRF) and associates with enhancer DNAs of the NF-κB site and CArG box. Oncogene 8: 2391–2397PubMedGoogle Scholar
  299. Ten RM, Blank V, Le Bail O, Kourilsky B, Israel A (1993): Two factors, IRF-1 and KBFI/NF-κB, cooperate during induction of MHC class I gene expression by interferon α/β or Newcastle disease virus. C R Acad Sci HI 316: 496–501Google Scholar
  300. Ten RM, Paya CV, Israël N, LeBail O, Mattei M-G, Virelizier J-L, Kourilsky P, Israël A (1992): The characterization of the promoter of the gene encoding the p50 subunit of NF-κB indicates that it participates in its own regulation. EMBO J 11: 195–203PubMedGoogle Scholar
  301. Tewari M, Dobrzanski P, Mohn KL, Cressman DE, Hsu J-C, Bravo R, Taub R (1992): Rapid induction in regenerating liver of RL/IF-1 (an IκB that inhibits NF-κB, RelB-p50, and c-Rel-p50) and PHF, a novel κB site-binding complex. Mol Cell Biol 12: 2898–2908PubMedGoogle Scholar
  302. Thanos D, Maniatis T (1992): The high mobility group protein HMG I(Y) is required for NF-κB-dependent virus induction of the human IFN-β gene. Cell 71: 777–789PubMedGoogle Scholar
  303. Thevenin C, Kim S-C, Rieckmann P, Fujiki H, Norcross MA, Sporn MB, Kehrl JH (1991): Induction of nuclear factor-κB and the human immunodeficiency virus long terminal repeat by okadaic acid, a specific inhibitor of phosphatases I and 2A. New Biologist 2: 793–800Google Scholar
  304. Toledano MB, Leonard WJ (1991): Modulation of transcription factor NF-κB binding activity by oxidation-reduction in vitro. Proc Natl Acad Sci USA 88: 4328–4332PubMedGoogle Scholar
  305. Toledano MB, Ghosh D, Trinh F, Leonard WJ (1993): N-terminal DNA-binding domains contribute to differential DNA-binding specificities of NF-κB p50 and p65. Mol Cell Biol 13: 852–860PubMedGoogle Scholar
  306. Trede NS, Castigli E, Geha RS, Chatila T (1993): Microbial superantigens induce NF-κB in the human monocytic cell line THP-1. J Immunol 150: 5604–5613PubMedGoogle Scholar
  307. Uckun FM, Schieven GL, Tuel-Ahlgren LM, Dibirdik I, Myers D, Ledbetter JA, Song CW (1993): Tyrosine phosphorylation is a mandatory proximal step in radiation-induced activation of the protein kinase C signaling pathway in human B-lymphocyte precursors. Proc Natl Acad Sci USA 90: 252–256PubMedGoogle Scholar
  308. Ueberla K, Lu YC, Chung E, Haseltine WA (1993): The NF-κB p65 promoter. J AIDS Res 6: 227–230Google Scholar
  309. Urban MB, Baeuerle PA (1990): The 65-kD subunit of NF-κB is a receptor for IκB and a modulator of DNA-binding specificity. Genes Develop 4: 1975–1984PubMedGoogle Scholar
  310. Verweij CL, Geerts M, Aarden LA (1991): Activation of interleukin-2 transcription via the T-cell surface molecule CD28 is mediated through an NF-κB-like response element.J Biol Chem 266: 14179–14182PubMedGoogle Scholar
  311. Voraberger G, Schafer R, Stratowa C (1991): Cloning of the human gene for intercellular adhesion molecule 1 and analysis of its 5’ regulatory region. Induction by cytokines and phorbol ester. J Immunol 147: 2777–2786PubMedGoogle Scholar
  312. Walker WH, Stein B, Ganchi PA, Hoffman JA, Kaufman PA, Ballard DW, Hannink M, Greene WC (1992): The v-rel oncogene: insights into the mechanism of transcriptional activation, repression and transformation. J Virol 66: 5018–5029PubMedGoogle Scholar
  313. Wasserman SA (1993): A conserved signal transduction pathway regulating the activity of the rel-like proteins dorsal and NF-κB. Mol Biol Cell 4: 767–771PubMedGoogle Scholar
  314. Watanabe M, Muramatsu M, Hirai H, Suzuki T (1993): HTLV-I encoded Tax in association with NF-κB precursor p105 enhances nuclear localization of NF-κB p50 and p65 in transfected cells. Oncogene 8: 2949–2958PubMedGoogle Scholar
  315. Wilhelmsen KC, Eggleton K, Temin HM (1984): Nucleic acid sequence of the oncogene v-rel in reticuloendotheliosis virus strain T and its cellular homolog, the protooncogene c-rel. J Virol 52: 172–182PubMedGoogle Scholar
  316. Wulczyn FG, Naumann M, Scheidereit C (1992): Candidate proto-oncogene bcl-3 encodes a subunit-specific inhibitor of transcription factor NF-κB. Nature 358: 597–599PubMedGoogle Scholar
  317. Xie QW, Kashiwabara Y, Nathan C (1994): Role of transcription factor NF-κB/Rel in induction of nitric oxide synthase. J Biol Chem 269: 4705–5708PubMedGoogle Scholar
  318. Xu X, Prorock C, Ishikawa H, Maldonado E (1993): Functional interaction of the v-Rel and c-Rel oncoproteins with the TATA-binding protein and association with transcription factor IIB. Mol Cell Biol 13: 6733–6741PubMedGoogle Scholar
  319. Yang Z, Costanzo M, Golde W, Kolesnick RN (1993): Tumor necrosis factor activation of the shingomyelin pathway signals nuclear factor kappa B translocation in tact HL-60 cells.J Biol Chem 268: 20520–20523PubMedGoogle Scholar
  320. Zabel U, Baeurle PA (1990): Purified human IκB can rapidly dissociate the complex of the NF-κB transcription factor with its cognate DNA. Cell 61: 255–265PubMedGoogle Scholar
  321. Zabel U, Henkel T, dos SantosSilva M, Baeuerle P (1993): Nuclear uptake control of NF-κB by MAD-3, and IκB protein present in the nucleus. EMBO J 12: 201–211PubMedGoogle Scholar
  322. Zhang Y, Broser M, Rom WN (1994): Activation of the interleukin-6 by Mycobacterium tuberculosis and lipopolysaccharide is mediated by nuclear factors NF-IL-6 and NF-kappa B. Proc Natl Acad Sci USA 91: 2225–2229PubMedGoogle Scholar
  323. Ziegler-Heitbrock HW, Sternsdorf T, Liese J, Belohradsky B, Weber C, Wedel A, Shreck R, Bauerle P, Strobel M (1993): Pyrrolidine dithiocarbamate inhibits NF-κB mobilization and TNF production in human monocytes. J Immunol 151: 6986–6993PubMedGoogle Scholar
  324. Zuniga-Pflucker JC, Schwartz ML, Lenardo MY (1993): Gene transcription in differentiating immature T cell receptor (neg) thymocytes resembles antigen-activated mature T cells. Medicine 178: 1139–1149Google Scholar

Copyright information

© Birkhäuser Boston 1995

Authors and Affiliations

  • Ulrich Siebenlist
  • Keith Brown
  • Guido Franzoso

There are no affiliations available

Personalised recommendations