Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Jun;87(12):4727–4731. doi: 10.1073/pnas.87.12.4727

Interaction of an NF-kappa B-like factor with a site upstream of the c-myc promoter.

M P Duyao 1, A J Buckler 1, G E Sonenshein 1
PMCID: PMC54190  PMID: 2191300

Abstract

The c-myc protooncogene has been implicated in control of growth and differentiation of mammalian cells. For instance, growth arrest is often preceded by reduction in c-myc mRNA and gene transcription. To elucidate the mechanisms of control of c-myc gene transcription, we have begun to characterize the interaction of nuclear factors with the 719-base-pair (bp) c-myc regulatory domain, located 1139-421 bp upstream of the P1 start site of the mouse gene. Nuclear extracts from exponentially growing WEHI 231 murine B-lymphoma cells formed multiple complexes in mobility-shift assays. Changes in complex distribution were observed in growth-arrested WEHI 231 cells, and a major site of this interaction mapped to a 21-bp sequence that is similar to the sequences recognized by the NF-kappa B family of proteins. Binding of NF-kappa B-like factors was demonstrated by oligonucleotide competition. Induction of complex formation upon 70Z/3 pre-B- to B-cell differentiation, enhancement of binding by GTP, and detergent-induced release of inhibitor protein suggested that NF-kappa B itself is one member of the family that can bind. Transfection of thymidine kinase-chloramphenicol acetyltransferase constructs containing the 21-bp c-myc sequence into Jurkat cells demonstrated increased chloramphenicol acetyltransferase activity upon phorbol ester and phytohemagglutinin treatment. These results suggest the involvement of NF-kappa B-like factors in the regulation of c-myc transcription.

Full text

PDF
4727

Images in this article

4728Image
on p.4728
4729Image
on p.4729
4729Image
on p.4729
4729Image
on p.4729
4730Image
on p.4730
4730Image
on p.4730
4730Image
on p.4730
4731Image
on p.4731

Selected References

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

  1. Atchison M. L., Perry R. P. The role of the kappa enhancer and its binding factor NF-kappa B in the developmental regulation of kappa gene transcription. Cell. 1987 Jan 16;48(1):121–128. doi: 10.1016/0092-8674(87)90362-x. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Baldwin A. S., Jr, Sharp P. A. Two transcription factors, NF-kappa B and H2TF1, interact with a single regulatory sequence in the class I major histocompatibility complex promoter. Proc Natl Acad Sci U S A. 1988 Feb;85(3):723–727. doi: 10.1073/pnas.85.3.723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ballard D. W., Böhnlein E., Lowenthal J. W., Wano Y., Franza B. R., Greene W. C. HTLV-I tax induces cellular proteins that activate the kappa B element in the IL-2 receptor alpha gene. Science. 1988 Sep 23;241(4873):1652–1655. doi: 10.1126/science.241.4873.1652. [DOI] [PubMed] [Google Scholar]
  5. Boyd A. W., Schrader J. W. The regulation of growth and differentiation of a murine B cell lymphoma. II. The inhibition of WEHI 231 by anti-immunoglobulin antibodies. J Immunol. 1981 Jun;126(6):2466–2469. [PubMed] [Google Scholar]
  6. Böhnlein E., Lowenthal J. W., Siekevitz M., Ballard D. W., Franza B. R., Greene W. C. The same inducible nuclear proteins regulates mitogen activation of both the interleukin-2 receptor-alpha gene and type 1 HIV. Cell. 1988 Jun 3;53(5):827–836. doi: 10.1016/0092-8674(88)90099-2. [DOI] [PubMed] [Google Scholar]
  7. Chung J., Sinn E., Reed R. R., Leder P. Trans-acting elements modulate expression of the human c-myc gene in Burkitt lymphoma cells. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7918–7922. doi: 10.1073/pnas.83.20.7918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Donoghue M., Ernst H., Wentworth B., Nadal-Ginard B., Rosenthal N. A muscle-specific enhancer is located at the 3' end of the myosin light-chain 1/3 gene locus. Genes Dev. 1988 Dec;2(12B):1779–1790. doi: 10.1101/gad.2.12b.1779. [DOI] [PubMed] [Google Scholar]
  9. Edbrooke M. R., Burt D. W., Cheshire J. K., Woo P. Identification of cis-acting sequences responsible for phorbol ester induction of human serum amyloid A gene expression via a nuclear factor kappaB-like transcription factor. Mol Cell Biol. 1989 May;9(5):1908–1916. doi: 10.1128/mcb.9.5.1908. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hay N., Bishop J. M., Levens D. Regulatory elements that modulate expression of human c-myc. Genes Dev. 1987 Sep;1(7):659–671. doi: 10.1101/gad.1.7.659. [DOI] [PubMed] [Google Scholar]
  11. Hoyos B., Ballard D. W., Böhnlein E., Siekevitz M., Greene W. C. Kappa B-specific DNA binding proteins: role in the regulation of human interleukin-2 gene expression. Science. 1989 Apr 28;244(4903):457–460. doi: 10.1126/science.2497518. [DOI] [PubMed] [Google Scholar]
  12. Kuwabara M. D., Sigman D. S. Footprinting DNA-protein complexes in situ following gel retardation assays using 1,10-phenanthroline-copper ion: Escherichia coli RNA polymerase-lac promoter complexes. Biochemistry. 1987 Nov 17;26(23):7234–7238. doi: 10.1021/bi00397a006. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Lenardo M. J., Kuang A., Gifford A., Baltimore D. NF-kappa B protein purification from bovine spleen: nucleotide stimulation and binding site specificity. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8825–8829. doi: 10.1073/pnas.85.23.8825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lenardo M., Pierce J. W., Baltimore D. Protein-binding sites in Ig gene enhancers determine transcriptional activity and inducibility. Science. 1987 Jun 19;236(4808):1573–1577. doi: 10.1126/science.3109035. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Levine R. A., McCormack J. E., Buckler A., Sonenshein G. E. Transcriptional and posttranscriptional control of c-myc gene expression in WEHI 231 cells. Mol Cell Biol. 1986 Nov;6(11):4112–4116. doi: 10.1128/mcb.6.11.4112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lieber M. R., Hesse J. E., Mizuuchi K., Gellert M. Developmental stage specificity of the lymphoid V(D)J recombination activity. Genes Dev. 1987 Oct;1(8):751–761. doi: 10.1101/gad.1.8.751. [DOI] [PubMed] [Google Scholar]
  20. Mason P. J., Elkington J. A., Lloyd M. M., Jones M. B., Williams J. G. Mutations downstream of the polyadenylation site of a Xenopus beta-globin mRNA affect the position but not the efficiency of 3' processing. Cell. 1986 Jul 18;46(2):263–270. doi: 10.1016/0092-8674(86)90743-9. [DOI] [PubMed] [Google Scholar]
  21. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  22. McCormack J. E., Pepe V. H., Kent R. B., Dean M., Marshak-Rothstein A., Sonenshein G. E. Specific regulation of c-myc oncogene expression in a murine B-cell lymphoma. Proc Natl Acad Sci U S A. 1984 Sep;81(17):5546–5550. doi: 10.1073/pnas.81.17.5546. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Queen C., Baltimore D. Immunoglobulin gene transcription is activated by downstream sequence elements. Cell. 1983 Jul;33(3):741–748. doi: 10.1016/0092-8674(83)90016-8. [DOI] [PubMed] [Google Scholar]
  25. Remmers E. F., Yang J. Q., Marcu K. B. A negative transcriptional control element located upstream of the murine c-myc gene. EMBO J. 1986 May;5(5):899–904. doi: 10.1002/j.1460-2075.1986.tb04301.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. 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]
  28. Siekevitz M., Josephs S. F., Dukovich M., Peffer N., Wong-Staal F., Greene W. C. Activation of the HIV-1 LTR by T cell mitogens and the trans-activator protein of HTLV-I. Science. 1987 Dec 11;238(4833):1575–1578. doi: 10.1126/science.2825351. [DOI] [PubMed] [Google Scholar]
  29. Strauss F., Varshavsky A. A protein binds to a satellite DNA repeat at three specific sites that would be brought into mutual proximity by DNA folding in the nucleosome. Cell. 1984 Jul;37(3):889–901. doi: 10.1016/0092-8674(84)90424-0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES