Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1995 Feb;15(2):943–953. doi: 10.1128/mcb.15.2.943

Characterization of mechanisms involved in transrepression of NF-kappa B by activated glucocorticoid receptors.

R I Scheinman 1, A Gualberto 1, C M Jewell 1, J A Cidlowski 1, A S Baldwin Jr 1
PMCID: PMC231982  PMID: 7823959

Abstract

Glucocorticoids are potent immunosuppressants which work in part by inhibiting cytokine gene transcription. We show here that NF-kappa B, an important regulator of numerous cytokine genes, is functionally inhibited by the synthetic glucocorticoid dexamethasone (DEX). In transfection experiments, DEX treatment in the presence of cotransfected glucocorticoid receptor (GR) inhibits NF-kappa B p65-mediated gene expression and p65 inhibits GR activation of a glucocorticoid response element. Evidence is presented for a direct interaction between GR and the NF-kappa B subunits p65 and p50. In addition, we demonstrate that the ability of p65, p50, and c-rel subunits to bind DNA is inhibited by DEX and GR. In HeLa cells, DEX activation of endogenous GR is sufficient to block tumor necrosis factor alpha or interleukin 1 activation of NF-kappa B at the levels of both DNA binding and transcriptional activation. DEX treatment of HeLa cells also results in a significant loss of nuclear p65 and a slight increase in cytoplasmic p65. These data reveal a second mechanism by which NF-kappa B activity may be regulated by DEX. We also report that RU486 treatment of wild-type GR and DEX treatment of a transactivation mutant of GR each can significantly inhibit p65 activity. In addition, we found that the zinc finger domain of GR is necessary for the inhibition of p65. This domain is also required for GR repression of AP-1. Surprisingly, while both AP-1 and NF-kappa B can be inhibited by activated GR, synergistic NF-kappa B/AP-1 activity is largely unaffected. These data suggest that NF-kappa B, AP-1, and GR interact in a complex regulatory network to modulate gene expression and that cross-coupling of NF-kappa B and GR plays an important role in glucocorticoid-mediated repression of cytokine transcription.

Full Text

The Full Text of this article is available as a PDF (418.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allgood V. E., Oakley R. H., Cidlowski J. A. Modulation by vitamin B6 of glucocorticoid receptor-mediated gene expression requires transcription factors in addition to the glucocorticoid receptor. J Biol Chem. 1993 Oct 5;268(28):20870–20876. [PubMed] [Google Scholar]
  2. Andersson S., Davis D. L., Dahlbäck H., Jörnvall H., Russell D. W. Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme. J Biol Chem. 1989 May 15;264(14):8222–8229. [PubMed] [Google Scholar]
  3. Arima N., Kuziel W. A., Grdina T. A., Greene W. C. IL-2-induced signal transduction involves the activation of nuclear NF-kappa B expression. J Immunol. 1992 Jul 1;149(1):83–91. [PubMed] [Google Scholar]
  4. Baeuerle P. A., Baltimore D. A 65-kappaD subunit of active NF-kappaB is required for inhibition of NF-kappaB by I kappaB. Genes Dev. 1989 Nov;3(11):1689–1698. doi: 10.1101/gad.3.11.1689. [DOI] [PubMed] [Google Scholar]
  5. Baeuerle P. A., Baltimore D. Activation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-kappa B transcription factor. Cell. 1988 Apr 22;53(2):211–217. doi: 10.1016/0092-8674(88)90382-0. [DOI] [PubMed] [Google Scholar]
  6. Baeuerle P. A., Baltimore D. I kappa B: a specific inhibitor of the NF-kappa B transcription factor. Science. 1988 Oct 28;242(4878):540–546. doi: 10.1126/science.3140380. [DOI] [PubMed] [Google Scholar]
  7. Baldwin A. S., Jr, Azizkhan J. C., Jensen D. E., Beg A. A., Coodly L. R. Induction of NF-kappa B DNA-binding activity during the G0-to-G1 transition in mouse fibroblasts. Mol Cell Biol. 1991 Oct;11(10):4943–4951. doi: 10.1128/mcb.11.10.4943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Beato M. Gene regulation by steroid hormones. Cell. 1989 Feb 10;56(3):335–344. doi: 10.1016/0092-8674(89)90237-7. [DOI] [PubMed] [Google Scholar]
  9. Beg A. A., Baldwin A. S., Jr Activation of multiple NF-kappa B/Rel DNA-binding complexes by tumor necrosis factor. Oncogene. 1994 May;9(5):1487–1492. [PubMed] [Google Scholar]
  10. Beg A. A., Finco T. S., Nantermet P. V., Baldwin A. S., Jr Tumor necrosis factor and interleukin-1 lead to phosphorylation and loss of I kappa B alpha: a mechanism for NF-kappa B activation. Mol Cell Biol. 1993 Jun;13(6):3301–3310. doi: 10.1128/mcb.13.6.3301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Beg A. A., Ruben S. M., Scheinman R. I., Haskill S., Rosen C. A., Baldwin A. S., Jr I kappa B interacts with the nuclear localization sequences of the subunits of NF-kappa B: a mechanism for cytoplasmic retention. Genes Dev. 1992 Oct;6(10):1899–1913. doi: 10.1101/gad.6.10.1899. [DOI] [PubMed] [Google Scholar]
  12. Blank V., Kourilsky P., Israël A. NF-kappa B and related proteins: Rel/dorsal homologies meet ankyrin-like repeats. Trends Biochem Sci. 1992 Apr;17(4):135–140. doi: 10.1016/0968-0004(92)90321-y. [DOI] [PubMed] [Google Scholar]
  13. Bours V., Villalobos J., Burd P. R., Kelly K., Siebenlist U. Cloning of a mitogen-inducible gene encoding a kappa B DNA-binding protein with homology to the rel oncogene and to cell-cycle motifs. Nature. 1990 Nov 1;348(6296):76–80. doi: 10.1038/348076a0. [DOI] [PubMed] [Google Scholar]
  14. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  15. Brown K., Park S., Kanno T., Franzoso G., Siebenlist U. Mutual regulation of the transcriptional activator NF-kappa B and its inhibitor, I kappa B-alpha. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2532–2536. doi: 10.1073/pnas.90.6.2532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Cheng Q., Cant C. A., Moll T., Hofer-Warbinek R., Wagner E., Birnstiel M. L., Bach F. H., de Martin R. NK-kappa B subunit-specific regulation of the I kappa B alpha promoter. J Biol Chem. 1994 May 6;269(18):13551–13557. [PubMed] [Google Scholar]
  17. Cidlowski J. A., Bellingham D. L., Powell-Oliver F. E., Lubahn D. B., Sar M. Novel antipeptide antibodies to the human glucocorticoid receptor: recognition of multiple receptor forms in vitro and distinct localization of cytoplasmic and nuclear receptors. Mol Endocrinol. 1990 Oct;4(10):1427–1437. doi: 10.1210/mend-4-10-1427. [DOI] [PubMed] [Google Scholar]
  18. Cogswell P. C., Scheinman R. I., Baldwin A. S., Jr Promoter of the human NF-kappa B p50/p105 gene. Regulation by NF-kappa B subunits and by c-REL. J Immunol. 1993 Apr 1;150(7):2794–2804. [PubMed] [Google Scholar]
  19. Cupps T. R., Fauci A. S. Corticosteroid-mediated immunoregulation in man. Immunol Rev. 1982;65:133–155. doi: 10.1111/j.1600-065x.1982.tb00431.x. [DOI] [PubMed] [Google Scholar]
  20. Diamond M. I., Miner J. N., Yoshinaga S. K., Yamamoto K. R. Transcription factor interactions: selectors of positive or negative regulation from a single DNA element. Science. 1990 Sep 14;249(4974):1266–1272. doi: 10.1126/science.2119054. [DOI] [PubMed] [Google Scholar]
  21. Drouin J., Sun Y. L., Chamberland M., Gauthier Y., De Léan A., Nemer M., Schmidt T. J. Novel glucocorticoid receptor complex with DNA element of the hormone-repressed POMC gene. EMBO J. 1993 Jan;12(1):145–156. doi: 10.1002/j.1460-2075.1993.tb05640.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Evans R. M. The steroid and thyroid hormone receptor superfamily. Science. 1988 May 13;240(4854):889–895. doi: 10.1126/science.3283939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ghosh S., Gifford A. M., Riviere L. R., Tempst P., Nolan G. P., Baltimore D. Cloning of the p50 DNA binding subunit of NF-kappa B: homology to rel and dorsal. Cell. 1990 Sep 7;62(5):1019–1029. doi: 10.1016/0092-8674(90)90276-k. [DOI] [PubMed] [Google Scholar]
  24. Gillis S., Crabtree G. R., Smith K. A. Glucocorticoid-induced inhibition of T cell growth factor production. I. The effect on mitogen-induced lymphocyte proliferation. J Immunol. 1979 Oct;123(4):1624–1631. [PubMed] [Google Scholar]
  25. Goldfeld A. E., Doyle C., Maniatis T. Human tumor necrosis factor alpha gene regulation by virus and lipopolysaccharide. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9769–9773. doi: 10.1073/pnas.87.24.9769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  28. Hansen S. K., Nerlov C., Zabel U., Verde P., Johnsen M., Baeuerle P. A., Blasi F. A novel complex between the p65 subunit of NF-kappa B and c-Rel binds to a DNA element involved in the phorbol ester induction of the human urokinase gene. EMBO J. 1992 Jan;11(1):205–213. doi: 10.1002/j.1460-2075.1992.tb05043.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Hiscott J., Marois J., Garoufalis J., D'Addario M., Roulston A., Kwan I., Pepin N., Lacoste J., Nguyen H., Bensi G. Characterization of a functional NF-kappa B site in the human interleukin 1 beta promoter: evidence for a positive autoregulatory loop. Mol Cell Biol. 1993 Oct;13(10):6231–6240. doi: 10.1128/mcb.13.10.6231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Inoue J., Kerr L. D., Rashid D., Davis N., Bose H. R., Jr, Verma I. M. Direct association of pp40/I kappa B beta with rel/NF-kappa B transcription factors: role of ankyrin repeats in the inhibition of DNA binding activity. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4333–4337. doi: 10.1073/pnas.89.10.4333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Jonat C., Rahmsdorf H. J., Park K. K., Cato A. C., Gebel S., Ponta H., Herrlich P. Antitumor promotion and antiinflammation: down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone. Cell. 1990 Sep 21;62(6):1189–1204. doi: 10.1016/0092-8674(90)90395-u. [DOI] [PubMed] [Google Scholar]
  32. Kang S. M., Tran A. C., Grilli M., Lenardo M. J. NF-kappa B subunit regulation in nontransformed CD4+ T lymphocytes. Science. 1992 Jun 5;256(5062):1452–1456. doi: 10.1126/science.1604322. [DOI] [PubMed] [Google Scholar]
  33. Kaszubska W., Hooft van Huijsduijnen R., Ghersa P., DeRaemy-Schenk A. M., Chen B. P., Hai T., DeLamarter J. F., Whelan J. Cyclic AMP-independent ATF family members interact with NF-kappa B and function in the activation of the E-selectin promoter in response to cytokines. Mol Cell Biol. 1993 Nov;13(11):7180–7190. doi: 10.1128/mcb.13.11.7180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Kawai S., Nishizawa M. New procedure for DNA transfection with polycation and dimethyl sulfoxide. Mol Cell Biol. 1984 Jun;4(6):1172–1174. doi: 10.1128/mcb.4.6.1172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Kawakami K., Scheidereit C., Roeder R. G. Identification and purification of a human immunoglobulin-enhancer-binding protein (NF-kappa B) that activates transcription from a human immunodeficiency virus type 1 promoter in vitro. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4700–4704. doi: 10.1073/pnas.85.13.4700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Kerppola T. K., Luk D., Curran T. Fos is a preferential target of glucocorticoid receptor inhibition of AP-1 activity in vitro. Mol Cell Biol. 1993 Jun;13(6):3782–3791. doi: 10.1128/mcb.13.6.3782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Kieran M., Blank V., Logeat F., Vandekerckhove J., Lottspeich F., Le Bail O., Urban M. B., Kourilsky P., Baeuerle P. A., Israël A. The DNA binding subunit of NF-kappa B is identical to factor KBF1 and homologous to the rel oncogene product. Cell. 1990 Sep 7;62(5):1007–1018. doi: 10.1016/0092-8674(90)90275-j. [DOI] [PubMed] [Google Scholar]
  38. Le Bail O., Schmidt-Ullrich R., Israël A. Promoter analysis of the gene encoding the I kappa B-alpha/MAD3 inhibitor of NF-kappa B: positive regulation by members of the rel/NF-kappa B family. EMBO J. 1993 Dec 15;12(13):5043–5049. doi: 10.1002/j.1460-2075.1993.tb06197.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Lenardo M. J., Baltimore D. NF-kappa B: a pleiotropic mediator of inducible and tissue-specific gene control. Cell. 1989 Jul 28;58(2):227–229. doi: 10.1016/0092-8674(89)90833-7. [DOI] [PubMed] [Google Scholar]
  40. Lenardo M. J., Fan C. M., Maniatis T., Baltimore D. The involvement of NF-kappa B in beta-interferon gene regulation reveals its role as widely inducible mediator of signal transduction. Cell. 1989 Apr 21;57(2):287–294. doi: 10.1016/0092-8674(89)90966-5. [DOI] [PubMed] [Google Scholar]
  41. Libermann T. A., Baltimore D. Activation of interleukin-6 gene expression through the NF-kappa B transcription factor. Mol Cell Biol. 1990 May;10(5):2327–2334. doi: 10.1128/mcb.10.5.2327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Lucibello F. C., Slater E. P., Jooss K. U., Beato M., Müller R. Mutual transrepression of Fos and the glucocorticoid receptor: involvement of a functional domain in Fos which is absent in FosB. EMBO J. 1990 Sep;9(9):2827–2834. doi: 10.1002/j.1460-2075.1990.tb07471.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Mercurio F., DiDonato J. A., Rosette C., Karin M. p105 and p98 precursor proteins play an active role in NF-kappa B-mediated signal transduction. Genes Dev. 1993 Apr;7(4):705–718. doi: 10.1101/gad.7.4.705. [DOI] [PubMed] [Google Scholar]
  44. Mercurio F., Didonato J., Rosette C., Karin M. Molecular cloning and characterization of a novel Rel/NF-kappa B family member displaying structural and functional homology to NF-kappa B p50/p105. DNA Cell Biol. 1992 Sep;11(7):523–537. doi: 10.1089/dna.1992.11.523. [DOI] [PubMed] [Google Scholar]
  45. Mukaida N., Morita M., Ishikawa Y., Rice N., Okamoto S., Kasahara T., Matsushima K. Novel mechanism of glucocorticoid-mediated gene repression. Nuclear factor-kappa B is target for glucocorticoid-mediated interleukin 8 gene repression. J Biol Chem. 1994 May 6;269(18):13289–13295. [PubMed] [Google Scholar]
  46. Neish A. S., Williams A. J., Palmer H. J., Whitley M. Z., Collins T. Functional analysis of the human vascular cell adhesion molecule 1 promoter. J Exp Med. 1992 Dec 1;176(6):1583–1593. doi: 10.1084/jem.176.6.1583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Nolan G. P., Baltimore D. The inhibitory ankyrin and activator Rel proteins. Curr Opin Genet Dev. 1992 Apr;2(2):211–220. doi: 10.1016/s0959-437x(05)80276-x. [DOI] [PubMed] [Google Scholar]
  48. Nolan G. P., Ghosh S., Liou H. C., Tempst P., Baltimore D. DNA binding and I kappa B inhibition of the cloned p65 subunit of NF-kappa B, a rel-related polypeptide. Cell. 1991 Mar 8;64(5):961–969. doi: 10.1016/0092-8674(91)90320-x. [DOI] [PubMed] [Google Scholar]
  49. O'Brien J. M., Cidlowski J. A. Interaction of pyridoxal phosphate with glucocorticoid receptors from HeLa S3 cells. J Steroid Biochem. 1981 Jan;14(1):9–18. doi: 10.1016/0022-4731(81)90186-2. [DOI] [PubMed] [Google Scholar]
  50. Ortí E., Mendel D. B., Smith L. I., Bodwell J. E., Munck A. A dynamic model of glucocorticoid receptor phosphorylation and cycling in intact cells. J Steroid Biochem. 1989;34(1-6):85–96. doi: 10.1016/0022-4731(89)90069-1. [DOI] [PubMed] [Google Scholar]
  51. Perkins N. D., Edwards N. L., Duckett C. S., Agranoff A. B., Schmid R. M., Nabel G. J. A cooperative interaction between NF-kappa B and Sp1 is required for HIV-1 enhancer activation. EMBO J. 1993 Sep;12(9):3551–3558. doi: 10.1002/j.1460-2075.1993.tb06029.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Plaut M. Lymphocyte hormone receptors. Annu Rev Immunol. 1987;5:621–669. doi: 10.1146/annurev.iy.05.040187.003201. [DOI] [PubMed] [Google Scholar]
  53. Ray A., Prefontaine K. E. Physical association and functional antagonism between the p65 subunit of transcription factor NF-kappa B and the glucocorticoid receptor. Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):752–756. doi: 10.1073/pnas.91.2.752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Rice N. R., MacKichan M. L., Israël A. The precursor of NF-kappa B p50 has I kappa B-like functions. Cell. 1992 Oct 16;71(2):243–253. doi: 10.1016/0092-8674(92)90353-e. [DOI] [PubMed] [Google Scholar]
  55. Ruben S. M., Dillon P. J., Schreck R., Henkel T., Chen C. H., Maher M., Baeuerle P. A., Rosen C. A. Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B. Science. 1991 Mar 22;251(5000):1490–1493. doi: 10.1126/science.2006423. [DOI] [PubMed] [Google Scholar]
  56. Ryseck R. P., Bull P., Takamiya M., Bours V., Siebenlist U., Dobrzanski P., Bravo R. RelB, a new Rel family transcription activator that can interact with p50-NF-kappa B. Mol Cell Biol. 1992 Feb;12(2):674–684. doi: 10.1128/mcb.12.2.674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Sakai D. D., Helms S., Carlstedt-Duke J., Gustafsson J. A., Rottman F. M., Yamamoto K. R. Hormone-mediated repression: a negative glucocorticoid response element from the bovine prolactin gene. Genes Dev. 1988 Sep;2(9):1144–1154. doi: 10.1101/gad.2.9.1144. [DOI] [PubMed] [Google Scholar]
  58. Scheinman R. I., Beg A. A., Baldwin A. S., Jr NF-kappa B p100 (Lyt-10) is a component of H2TF1 and can function as an I kappa B-like molecule. Mol Cell Biol. 1993 Oct;13(10):6089–6101. doi: 10.1128/mcb.13.10.6089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Schmid R. M., Perkins N. D., Duckett C. S., Andrews P. C., Nabel G. J. Cloning of an NF-kappa B subunit which stimulates HIV transcription in synergy with p65. Nature. 1991 Aug 22;352(6337):733–736. doi: 10.1038/352733a0. [DOI] [PubMed] [Google Scholar]
  60. Schmitz M. L., Baeuerle P. A. The p65 subunit is responsible for the strong transcription activating potential of NF-kappa B. EMBO J. 1991 Dec;10(12):3805–3817. doi: 10.1002/j.1460-2075.1991.tb04950.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Schreck R., Baeuerle P. A. NF-kappa B as inducible transcriptional activator of the granulocyte-macrophage colony-stimulating factor gene. Mol Cell Biol. 1990 Mar;10(3):1281–1286. doi: 10.1128/mcb.10.3.1281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Schreck R., Rieber P., Baeuerle P. A. Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1. EMBO J. 1991 Aug;10(8):2247–2258. doi: 10.1002/j.1460-2075.1991.tb07761.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Schüle R., Rangarajan P., Kliewer S., Ransone L. J., Bolado J., Yang N., Verma I. M., Evans R. M. Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor. Cell. 1990 Sep 21;62(6):1217–1226. doi: 10.1016/0092-8674(90)90397-w. [DOI] [PubMed] [Google Scholar]
  64. Sen R., Baltimore D. Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell. 1986 Dec 26;47(6):921–928. doi: 10.1016/0092-8674(86)90807-x. [DOI] [PubMed] [Google Scholar]
  65. Sen R., Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell. 1986 Aug 29;46(5):705–716. doi: 10.1016/0092-8674(86)90346-6. [DOI] [PubMed] [Google Scholar]
  66. Shibuya H., Taniguchi T. Identification of multiple cis-elements and trans-acting factors involved in the induced expression of human IL-2 gene. Nucleic Acids Res. 1989 Nov 25;17(22):9173–9184. doi: 10.1093/nar/17.22.9173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Shimizu H., Mitomo K., Watanabe T., Okamoto S., Yamamoto K. Involvement of a NF-kappa B-like transcription factor in the activation of the interleukin-6 gene by inflammatory lymphokines. Mol Cell Biol. 1990 Feb;10(2):561–568. doi: 10.1128/mcb.10.2.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Smith K. A. T-cell growth factor. Immunol Rev. 1980;51:337–357. doi: 10.1111/j.1600-065x.1980.tb00327.x. [DOI] [PubMed] [Google Scholar]
  69. Stein B., Baldwin A. S., Jr, Ballard D. W., Greene W. C., Angel P., Herrlich P. Cross-coupling of the NF-kappa B p65 and Fos/Jun transcription factors produces potentiated biological function. EMBO J. 1993 Oct;12(10):3879–3891. doi: 10.1002/j.1460-2075.1993.tb06066.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Stein B., Cogswell P. C., Baldwin A. S., Jr Functional and physical associations between NF-kappa B and C/EBP family members: a Rel domain-bZIP interaction. Mol Cell Biol. 1993 Jul;13(7):3964–3974. doi: 10.1128/mcb.13.7.3964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Sun S. C., Ganchi P. A., Ballard D. W., Greene W. C. NF-kappa B controls expression of inhibitor I kappa B alpha: evidence for an inducible autoregulatory pathway. Science. 1993 Mar 26;259(5103):1912–1915. doi: 10.1126/science.8096091. [DOI] [PubMed] [Google Scholar]
  72. Taniguchi T. Regulation of cytokine gene expression. Annu Rev Immunol. 1988;6:439–464. doi: 10.1146/annurev.iy.06.040188.002255. [DOI] [PubMed] [Google Scholar]
  73. Ten R. M., Paya C. V., Israël N., Le Bail O., Mattei M. G., Virelizier J. L., Kourilsky P., Israël A. The characterization of the promoter of the gene encoding the p50 subunit of NF-kappa B indicates that it participates in its own regulation. EMBO J. 1992 Jan;11(1):195–203. doi: 10.1002/j.1460-2075.1992.tb05042.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Ullman K. S., Northrop J. P., Verweij C. L., Crabtree G. R. Transmission of signals from the T lymphocyte antigen receptor to the genes responsible for cell proliferation and immune function: the missing link. Annu Rev Immunol. 1990;8:421–452. doi: 10.1146/annurev.iy.08.040190.002225. [DOI] [PubMed] [Google Scholar]
  75. Urban M. B., Schreck R., Baeuerle P. A. NF-kappa B contacts DNA by a heterodimer of the p50 and p65 subunit. EMBO J. 1991 Jul;10(7):1817–1825. doi: 10.1002/j.1460-2075.1991.tb07707.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Yamamoto K. R. Steroid receptor regulated transcription of specific genes and gene networks. Annu Rev Genet. 1985;19:209–252. doi: 10.1146/annurev.ge.19.120185.001233. [DOI] [PubMed] [Google Scholar]
  77. Yang-Yen H. F., Chambard J. C., Sun Y. L., Smeal T., Schmidt T. J., Drouin J., Karin M. Transcriptional interference between c-Jun and the glucocorticoid receptor: mutual inhibition of DNA binding due to direct protein-protein interaction. Cell. 1990 Sep 21;62(6):1205–1215. doi: 10.1016/0092-8674(90)90396-v. [DOI] [PubMed] [Google Scholar]
  78. Zhang Y. H., Lin J. X., Vilcek J. Interleukin-6 induction by tumor necrosis factor and interleukin-1 in human fibroblasts involves activation of a nuclear factor binding to a kappa B-like sequence. Mol Cell Biol. 1990 Jul;10(7):3818–3823. doi: 10.1128/mcb.10.7.3818. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES