Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1994 Dec;14(12):7695–7703. doi: 10.1128/mcb.14.12.7695

Transcriptional regulation of NF-kappa B2: evidence for kappa B-mediated positive and negative autoregulation.

S Liptay 1, R M Schmid 1, E G Nabel 1, G J Nabel 1
PMCID: PMC359311  PMID: 7969113

Abstract

NF-kappa B is an inducible transcription factor complex which regulates the expression of a variety of genes which are involved in the immune, inflammatory, and acute-phase responses. The maintenance of NF-kappa B activity in stimulated cells requires ongoing protein synthesis, suggesting several modes of regulation. In this report, we have characterized the transcriptional regulation of one family member, NF-kappa B2. The genomic structure and sequence of NF-kappa B2 revealed the presence of two promoters and at least four kappa B regulatory elements, which mediate responsiveness to phorbol myristate acetate and tumor necrosis factor alpha. Similar to other NF-kappa B family members, NF-kappa B2 is positively autoregulated. In contrast to other family members, we find that kappa B elements in the NFKB2 promoter can also mediate transcriptional repression in the absence of NF-kappa B. We identified a nuclear complex which binds specifically to a subset of kappa B-related sites but not to the canonical kappa B element. Because of its putative inhibitory or repressive effect, this binding activity has been termed Rep-kappa B. This mechanism of repressing basal NF-kappa B2 transcription in an inactivated state enables the cell to tightly control NF-kappa B2 activity. These data demonstrate that a novel mode of kappa B-dependent regulation is mediated by specific kappa B sites in the NFKB2 promoter.

Full text

PDF
7695

Images in this article

7696Image
on p.7696
7699Image
on p.7699
7701Image
on p.7701
7702Image
on p.7702
7702Image
on p.7702

Selected References

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

  1. 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]
  2. 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]
  3. Brownell E., Mittereder N., Rice N. R. A human rel proto-oncogene cDNA containing an Alu fragment as a potential coding exon. Oncogene. 1989 Jul;4(7):935–942. [PubMed] [Google Scholar]
  4. 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]
  5. Duckett C. S., Perkins N. D., Kowalik T. F., Schmid R. M., Huang E. S., Baldwin A. S., Jr, Nabel G. J. Dimerization of NF-KB2 with RelA(p65) regulates DNA binding, transcriptional activation, and inhibition by an I kappa B-alpha (MAD-3). Mol Cell Biol. 1993 Mar;13(3):1315–1322. doi: 10.1128/mcb.13.3.1315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Griffin G. E., Leung K., Folks T. M., Kunkel S., Nabel G. J. Activation of HIV gene expression during monocyte differentiation by induction of NF-kappa B. Nature. 1989 May 4;339(6219):70–73. doi: 10.1038/339070a0. [DOI] [PubMed] [Google Scholar]
  8. Hohmann H. P., Remy R., Scheidereit C., van Loon A. P. Maintenance of NF-kappa B activity is dependent on protein synthesis and the continuous presence of external stimuli. Mol Cell Biol. 1991 Jan;11(1):259–266. doi: 10.1128/mcb.11.1.259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Leung K., Nabel G. J. HTLV-1 transactivator induces interleukin-2 receptor expression through an NF-kappa B-like factor. Nature. 1988 Jun 23;333(6175):776–778. doi: 10.1038/333776a0. [DOI] [PubMed] [Google Scholar]
  11. Liptay S., Schmid R. M., Perkins N. D., Meltzer P., Altherr M. R., McPherson J. D., Wasmuth J. J., Nabel G. J. Related subunits of NF-kappa B map to two distinct loci associated with translocations in leukemia, NFKB1 and NFKB2. Genomics. 1992 Jun;13(2):287–292. doi: 10.1016/0888-7543(92)90244-m. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Nabel G., Baltimore D. An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature. 1987 Apr 16;326(6114):711–713. doi: 10.1038/326711a0. [DOI] [PubMed] [Google Scholar]
  14. Neri A., Chang C. C., Lombardi L., Salina M., Corradini P., Maiolo A. T., Chaganti R. S., Dalla-Favera R. B cell lymphoma-associated chromosomal translocation involves candidate oncogene lyt-10, homologous to NF-kappa B p50. Cell. 1991 Dec 20;67(6):1075–1087. doi: 10.1016/0092-8674(91)90285-7. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Padgett R. A., Grabowski P. J., Konarska M. M., Seiler S., Sharp P. A. Splicing of messenger RNA precursors. Annu Rev Biochem. 1986;55:1119–1150. doi: 10.1146/annurev.bi.55.070186.005351. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. 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]
  20. 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]
  21. 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]
  22. 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]
  23. 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]
  24. Thanos D., Maniatis T. The high mobility group protein HMG I(Y) is required for NF-kappa B-dependent virus induction of the human IFN-beta gene. Cell. 1992 Nov 27;71(5):777–789. doi: 10.1016/0092-8674(92)90554-p. [DOI] [PubMed] [Google Scholar]

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

RESOURCES