Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1995 Jul;15(7):3523–3530. doi: 10.1128/mcb.15.7.3523

Overexpression of RelA in transgenic mouse thymocytes: specific increase in levels of the inhibitor protein I kappa B alpha.

P Perez 1, S A Lira 1, R Bravo 1
PMCID: PMC230589  PMID: 7791759

Abstract

RelA (p65) is one of the strongest activators of the Rel/NF-kappa B family. As a first step to elucidate the mechanisms that regulate its activity in vivo, we have generated transgenic mice overexpressing RelA in the thymus. Although the levels of RelA were significantly increased in thymocytes of transgenic mice, the overall NF-kappa B-binding activity in unstimulated cells was not augmented compared with that in control thymocytes. This could be explained by the dramatic increase of endogenous I kappa B alpha levels observed in RelA-overexpressing cells in both cytoplasmic and nuclear compartments. The ikba mRNA levels were not augmented by overexpressed RelA, but I kappa B alpha inhibitor was found to be stabilized through association with RelA. Although a fraction of RelA was associated with cytoplasmic p105, no changes in the precursor levels were observed. Upon stimulation of RelA-overexpressing thymocytes with phorbol 12-myristate 13-acetate and lectin (phytohemaglutinin), different kappa B-binding complexes, including RelA homodimers, were partially released from I kappa B alpha. Association of RelA with I kappa B alpha prevented complete degradation of the inhibitor. No effect of phorbol 12-myristate 13-acetate-lectin treatment was detected on RelA associated with p105. Our data indicate that cytoplasmic retention of overexpressed RelA by I kappa B alpha is the major in vivo mechanism controlling the potential excess of NF-kappa B activity in long-term RelA-overexpressing thymocytes.

Full Text

The Full Text of this article is available as a PDF (413.7 KB).

Selected References

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

  1. Allen J. M., Forbush K. A., Perlmutter R. M. Functional dissection of the lck proximal promoter. Mol Cell Biol. 1992 Jun;12(6):2758–2768. doi: 10.1128/mcb.12.6.2758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baeuerle P. A., Henkel T. Function and activation of NF-kappa B in the immune system. Annu Rev Immunol. 1994;12:141–179. doi: 10.1146/annurev.iy.12.040194.001041. [DOI] [PubMed] [Google Scholar]
  3. Beg A. A., Baldwin A. S., Jr The I kappa B proteins: multifunctional regulators of Rel/NF-kappa B transcription factors. Genes Dev. 1993 Nov;7(11):2064–2070. doi: 10.1101/gad.7.11.2064. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. 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]
  7. Bose H. R., Jr The Rel family: models for transcriptional regulation and oncogenic transformation. Biochim Biophys Acta. 1992 Sep 14;1114(1):1–17. doi: 10.1016/0304-419x(92)90002-g. [DOI] [PubMed] [Google Scholar]
  8. Bours V., Burd P. R., Brown K., Villalobos J., Park S., Ryseck R. P., Bravo R., Kelly K., Siebenlist U. A novel mitogen-inducible gene product related to p50/p105-NF-kappa B participates in transactivation through a kappa B site. Mol Cell Biol. 1992 Feb;12(2):685–695. doi: 10.1128/mcb.12.2.685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Carrasco D., Ryseck R. P., Bravo R. Expression of relB transcripts during lymphoid organ development: specific expression in dendritic antigen-presenting cells. Development. 1993 Aug;118(4):1221–1231. doi: 10.1242/dev.118.4.1221. [DOI] [PubMed] [Google Scholar]
  11. Carrasco D., Weih F., Bravo R. Developmental expression of the mouse c-rel proto-oncogene in hematopoietic organs. Development. 1994 Oct;120(10):2991–3004. doi: 10.1242/dev.120.10.2991. [DOI] [PubMed] [Google Scholar]
  12. Chiao P. J., Miyamoto S., Verma I. M. Autoregulation of I kappa B alpha activity. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):28–32. doi: 10.1073/pnas.91.1.28. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Cressman D. E., Taub R. I kappa B alpha can localize in the nucleus but shows no direct transactivation potential. Oncogene. 1993 Sep;8(9):2567–2573. [PubMed] [Google Scholar]
  15. Dobrzanski P., Ryseck R. P., Bravo R. Both N- and C-terminal domains of RelB are required for full transactivation: role of the N-terminal leucine zipper-like motif. Mol Cell Biol. 1993 Mar;13(3):1572–1582. doi: 10.1128/mcb.13.3.1572. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Dobrzanski P., Ryseck R. P., Bravo R. Specific inhibition of RelB/p52 transcriptional activity by the C-terminal domain of p100. Oncogene. 1995 Mar 2;10(5):1003–1007. [PubMed] [Google Scholar]
  17. Finco T. S., Baldwin A. S., Jr Kappa B site-dependent induction of gene expression by diverse inducers of nuclear factor kappa B requires Raf-1. J Biol Chem. 1993 Aug 25;268(24):17676–17679. [PubMed] [Google Scholar]
  18. Frantz B., Nordby E. C., Bren G., Steffan N., Paya C. V., Kincaid R. L., Tocci M. J., O'Keefe S. J., O'Neill E. A. Calcineurin acts in synergy with PMA to inactivate I kappa B/MAD3, an inhibitor of NF-kappa B. EMBO J. 1994 Feb 15;13(4):861–870. doi: 10.1002/j.1460-2075.1994.tb06329.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ganchi P. A., Sun S. C., Greene W. C., Ballard D. W. A novel NF-kappa B complex containing p65 homodimers: implications for transcriptional control at the level of subunit dimerization. Mol Cell Biol. 1993 Dec;13(12):7826–7835. doi: 10.1128/mcb.13.12.7826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gilmore T. D., Morin P. J. The I kappa B proteins: members of a multifunctional family. Trends Genet. 1993 Dec;9(12):427–433. doi: 10.1016/0168-9525(93)90106-r. [DOI] [PubMed] [Google Scholar]
  21. Gilmore T. D. Role of rel family genes in normal and malignant lymphoid cell growth. Cancer Surv. 1992;15:69–87. [PubMed] [Google Scholar]
  22. Greaves D. R., Wilson F. D., Lang G., Kioussis D. Human CD2 3'-flanking sequences confer high-level, T cell-specific, position-independent gene expression in transgenic mice. Cell. 1989 Mar 24;56(6):979–986. doi: 10.1016/0092-8674(89)90631-4. [DOI] [PubMed] [Google Scholar]
  23. Grilli M., Chiu J. J., Lenardo M. J. NF-kappa B and Rel: participants in a multiform transcriptional regulatory system. Int Rev Cytol. 1993;143:1–62. doi: 10.1016/s0074-7696(08)61873-2. [DOI] [PubMed] [Google Scholar]
  24. Grimm S., Baeuerle P. A. The inducible transcription factor NF-kappa B: structure-function relationship of its protein subunits. Biochem J. 1993 Mar 1;290(Pt 2):297–308. doi: 10.1042/bj2900297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hansen S. K., Baeuerle P. A., Blasi F. Purification, reconstitution, and I kappa B association of the c-Rel-p65 (RelA) complex, a strong activator of transcription. Mol Cell Biol. 1994 Apr;14(4):2593–2603. doi: 10.1128/mcb.14.4.2593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Henkel T., Machleidt T., Alkalay I., Krönke M., Ben-Neriah Y., Baeuerle P. A. Rapid proteolysis of I kappa B-alpha is necessary for activation of transcription factor NF-kappa B. Nature. 1993 Sep 9;365(6442):182–185. doi: 10.1038/365182a0. [DOI] [PubMed] [Google Scholar]
  28. Henkel T., Zabel U., van Zee K., Müller J. M., Fanning E., Baeuerle P. A. Intramolecular masking of the nuclear location signal and dimerization domain in the precursor for the p50 NF-kappa B subunit. Cell. 1992 Mar 20;68(6):1121–1133. doi: 10.1016/0092-8674(92)90083-o. [DOI] [PubMed] [Google Scholar]
  29. Inoue J., Kerr L. D., Kakizuka A., Verma I. M. I kappa B gamma, a 70 kd protein identical to the C-terminal half of p110 NF-kappa B: a new member of the I kappa B family. Cell. 1992 Mar 20;68(6):1109–1120. doi: 10.1016/0092-8674(92)90082-n. [DOI] [PubMed] [Google Scholar]
  30. Kerr L. D., Inoue J., Davis N., Link E., Baeuerle P. A., Bose H. R., Jr, Verma I. M. The rel-associated pp40 protein prevents DNA binding of Rel and NF-kappa B: relationship with I kappa B beta and regulation by phosphorylation. Genes Dev. 1991 Aug;5(8):1464–1476. doi: 10.1101/gad.5.8.1464. [DOI] [PubMed] [Google Scholar]
  31. Kretzschmar M., Meisterernst M., Scheidereit C., Li G., Roeder R. G. Transcriptional regulation of the HIV-1 promoter by NF-kappa B in vitro. Genes Dev. 1992 May;6(5):761–774. doi: 10.1101/gad.6.5.761. [DOI] [PubMed] [Google Scholar]
  32. Kunsch C., Rosen C. A. NF-kappa B subunit-specific regulation of the interleukin-8 promoter. Mol Cell Biol. 1993 Oct;13(10):6137–6146. doi: 10.1128/mcb.13.10.6137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Kunsch C., Ruben S. M., Rosen C. A. Selection of optimal kappa B/Rel DNA-binding motifs: interaction of both subunits of NF-kappa B with DNA is required for transcriptional activation. Mol Cell Biol. 1992 Oct;12(10):4412–4421. doi: 10.1128/mcb.12.10.4412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Laird P. W., Zijderveld A., Linders K., Rudnicki M. A., Jaenisch R., Berns A. Simplified mammalian DNA isolation procedure. Nucleic Acids Res. 1991 Aug 11;19(15):4293–4293. doi: 10.1093/nar/19.15.4293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Lang G., Mamalaki C., Greenberg D., Yannoutsos N., Kioussis D. Deletion analysis of the human CD2 gene locus control region in transgenic mice. Nucleic Acids Res. 1991 Nov 11;19(21):5851–5856. doi: 10.1093/nar/19.21.5851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. 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]
  37. Lernbecher T., Müller U., Wirth T. Distinct NF-kappa B/Rel transcription factors are responsible for tissue-specific and inducible gene activation. Nature. 1993 Oct 21;365(6448):767–770. doi: 10.1038/365767a0. [DOI] [PubMed] [Google Scholar]
  38. Li C. C., Dai R. M., Chen E., Longo D. L. Phosphorylation of NF-KB1-p50 is involved in NF-kappa B activation and stable DNA binding. J Biol Chem. 1994 Dec 2;269(48):30089–30092. [PubMed] [Google Scholar]
  39. Li S., Sedivy J. M. Raf-1 protein kinase activates the NF-kappa B transcription factor by dissociating the cytoplasmic NF-kappa B-I kappa B complex. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9247–9251. doi: 10.1073/pnas.90.20.9247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Liou H. C., Baltimore D. Regulation of the NF-kappa B/rel transcription factor and I kappa B inhibitor system. Curr Opin Cell Biol. 1993 Jun;5(3):477–487. doi: 10.1016/0955-0674(93)90014-h. [DOI] [PubMed] [Google Scholar]
  41. Liptay S., Schmid R. M., Nabel E. G., Nabel G. J. Transcriptional regulation of NF-kappa B2: evidence for kappa B-mediated positive and negative autoregulation. Mol Cell Biol. 1994 Dec;14(12):7695–7703. doi: 10.1128/mcb.14.12.7695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Mann J. R., McMahon A. P. Factors influencing frequency production of transgenic mice. Methods Enzymol. 1993;225:771–781. doi: 10.1016/0076-6879(93)25049-8. [DOI] [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. Meyer R., Hatada E. N., Hohmann H. P., Haiker M., Bartsch C., Röthlisberger U., Lahm H. W., Schlaeger E. J., van Loon A. P., Scheidereit C. Cloning of the DNA-binding subunit of human nuclear factor kappa B: the level of its mRNA is strongly regulated by phorbol ester or tumor necrosis factor alpha. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):966–970. doi: 10.1073/pnas.88.3.966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Morin P. J., Gilmore T. D. The C terminus of the NF-kappa B p50 precursor and an I kappa B isoform contain transcription activation domains. Nucleic Acids Res. 1992 May 25;20(10):2453–2458. doi: 10.1093/nar/20.10.2453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Narayanan R., Higgins K. A., Perez J. R., Coleman T. A., Rosen C. A. Evidence for differential functions of the p50 and p65 subunits of NF-kappa B with a cell adhesion model. Mol Cell Biol. 1993 Jun;13(6):3802–3810. doi: 10.1128/mcb.13.6.3802. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Naumann M., Wulczyn F. G., Scheidereit C. The NF-kappa B precursor p105 and the proto-oncogene product Bcl-3 are I kappa B molecules and control nuclear translocation of NF-kappa B. EMBO J. 1993 Jan;12(1):213–222. doi: 10.1002/j.1460-2075.1993.tb05647.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. 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]
  50. 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]
  51. Palombella V. J., Rando O. J., Goldberg A. L., Maniatis T. The ubiquitin-proteasome pathway is required for processing the NF-kappa B1 precursor protein and the activation of NF-kappa B. Cell. 1994 Sep 9;78(5):773–785. doi: 10.1016/s0092-8674(94)90482-0. [DOI] [PubMed] [Google Scholar]
  52. Perkins N. D., Schmid R. M., Duckett C. S., Leung K., Rice N. R., Nabel G. J. Distinct combinations of NF-kappa B subunits determine the specificity of transcriptional activation. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1529–1533. doi: 10.1073/pnas.89.5.1529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Rice N. R., Ernst M. K. In vivo control of NF-kappa B activation by I kappa B alpha. EMBO J. 1993 Dec;12(12):4685–4695. doi: 10.1002/j.1460-2075.1993.tb06157.x. [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. 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]
  56. 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]
  57. 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]
  58. Schreiber E., Matthias P., Müller M. M., Schaffner W. Rapid detection of octamer binding proteins with 'mini-extracts', prepared from a small number of cells. Nucleic Acids Res. 1989 Aug 11;17(15):6419–6419. doi: 10.1093/nar/17.15.6419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Scott M. L., Fujita T., Liou H. C., Nolan G. P., Baltimore D. The p65 subunit of NF-kappa B regulates I kappa B by two distinct mechanisms. Genes Dev. 1993 Jul;7(7A):1266–1276. doi: 10.1101/gad.7.7a.1266. [DOI] [PubMed] [Google Scholar]
  60. Sha W. C., Liou H. C., Tuomanen E. I., Baltimore D. Targeted disruption of the p50 subunit of NF-kappa B leads to multifocal defects in immune responses. Cell. 1995 Jan 27;80(2):321–330. doi: 10.1016/0092-8674(95)90415-8. [DOI] [PubMed] [Google Scholar]
  61. Shu H. B., Agranoff A. B., Nabel E. G., Leung K., Duckett C. S., Neish A. S., Collins T., Nabel G. J. Differential regulation of vascular cell adhesion molecule 1 gene expression by specific NF-kappa B subunits in endothelial and epithelial cells. Mol Cell Biol. 1993 Oct;13(10):6283–6289. doi: 10.1128/mcb.13.10.6283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. 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]
  63. Sun S. C., Ganchi P. A., Béraud C., Ballard D. W., Greene W. C. Autoregulation of the NF-kappa B transactivator RelA (p65) by multiple cytoplasmic inhibitors containing ankyrin motifs. Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1346–1350. doi: 10.1073/pnas.91.4.1346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. 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]
  65. Tewari M., Dobrzanski P., Mohn K. L., Cressman D. E., Hsu J. C., Bravo R., Taub R. Rapid induction in regenerating liver of RL/IF-1 (an I kappa B that inhibits NF-kappa B, RelB-p50, and c-Rel-p50) and PHF, a novel kappa B site-binding complex. Mol Cell Biol. 1992 Jun;12(6):2898–2908. doi: 10.1128/mcb.12.6.2898. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Traenckner E. B., Wilk S., Baeuerle P. A. A proteasome inhibitor prevents activation of NF-kappa B and stabilizes a newly phosphorylated form of I kappa B-alpha that is still bound to NF-kappa B. EMBO J. 1994 Nov 15;13(22):5433–5441. doi: 10.1002/j.1460-2075.1994.tb06878.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. 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]
  68. Weih F., Carrasco D., Bravo R. Constitutive and inducible Rel/NF-kappa B activities in mouse thymus and spleen. Oncogene. 1994 Nov;9(11):3289–3297. [PubMed] [Google Scholar]
  69. Weih F., Carrasco D., Durham S. K., Barton D. S., Rizzo C. A., Ryseck R. P., Lira S. A., Bravo R. Multiorgan inflammation and hematopoietic abnormalities in mice with a targeted disruption of RelB, a member of the NF-kappa B/Rel family. Cell. 1995 Jan 27;80(2):331–340. doi: 10.1016/0092-8674(95)90416-6. [DOI] [PubMed] [Google Scholar]
  70. Zabel U., Henkel T., Silva M. S., Baeuerle P. A. Nuclear uptake control of NF-kappa B by MAD-3, an I kappa B protein present in the nucleus. EMBO J. 1993 Jan;12(1):201–211. doi: 10.1002/j.1460-2075.1993.tb05646.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. de Martin R., Vanhove B., Cheng Q., Hofer E., Csizmadia V., Winkler H., Bach F. H. Cytokine-inducible expression in endothelial cells of an I kappa B alpha-like gene is regulated by NF kappa B. EMBO J. 1993 Jul;12(7):2773–2779. doi: 10.1002/j.1460-2075.1993.tb05938.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES