Skip to main content
PMC home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1992 Feb 25;20(4):897–902. doi: 10.1093/nar/20.4.897

Upstream regions of the c-jun promoter regulate phorbol ester-induced transcription in U937 leukemic cells.

T Unlap 1, C C Franklin 1, F Wagner 1, A S Kraft 1
PMCID: PMC312034  PMID: 1542579

Abstract

To understand the mechanism by which phorbol esters (PMA) stimulate c-jun transcription in human leukemic cell line U937, we have mutated specific enhancer sequences within the c-jun promoter. We find in the region of DNA from -132 to +170 containing Sp1, C-TF and AP-1 sequences that mutation of the AP-1 sequence alone is not sufficient to abrogate transcription, and mutation of the Sp1 sequence increases transcription 4-fold. Although mutation of the CTF site had no effect, CTF and AP-1 mutations together totally abrogate PMA-induced transcription. In comparison mutations of either of these sites alone or together in a construct containing -1639/+740 of the c-jun promoter had no effect on transcription. Because this data suggested the possibility of other upstream control regions, we sequenced the promoter from -142 to -1639. This sequence demonstrates a greater than 70% homology between human, and mouse c-jun promoters for the region from -142 to -441, and a second AP-1-like site in the -183 to -192 region. Mutation of this site did not influence transcription by PMA. By making constructs containing varying portions of the promoter, we have identified the region between -142 and -711 to be responsible for mediating PMA-induced c-jun transcription.

Full text

PDF
900

Images in this article

899Image
on p.899
901Image
on p.901

Selected References

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

  1. Adunyah S. E., Unlap T. M., Wagner F., Kraft A. S. Regulation of c-jun expression and AP-1 enhancer activity by granulocyte-macrophage colony-stimulating factor. J Biol Chem. 1991 Mar 25;266(9):5670–5675. [PubMed] [Google Scholar]
  2. Angel P., Baumann I., Stein B., Delius H., Rahmsdorf H. J., Herrlich P. 12-O-tetradecanoyl-phorbol-13-acetate induction of the human collagenase gene is mediated by an inducible enhancer element located in the 5'-flanking region. Mol Cell Biol. 1987 Jun;7(6):2256–2266. doi: 10.1128/mcb.7.6.2256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Angel P., Hattori K., Smeal T., Karin M. The jun proto-oncogene is positively autoregulated by its product, Jun/AP-1. Cell. 1988 Dec 2;55(5):875–885. doi: 10.1016/0092-8674(88)90143-2. [DOI] [PubMed] [Google Scholar]
  4. Angel P., Imagawa M., Chiu R., Stein B., Imbra R. J., Rahmsdorf H. J., Jonat C., Herrlich P., Karin M. Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell. 1987 Jun 19;49(6):729–739. doi: 10.1016/0092-8674(87)90611-8. [DOI] [PubMed] [Google Scholar]
  5. Auble D. T., Brinckerhoff C. E. The AP-1 sequence is necessary but not sufficient for phorbol induction of collagenase in fibroblasts. Biochemistry. 1991 May 7;30(18):4629–4635. doi: 10.1021/bi00232a039. [DOI] [PubMed] [Google Scholar]
  6. Chiu R., Imagawa M., Imbra R. J., Bockoven J. R., Karin M. Multiple cis- and trans-acting elements mediate the transcriptional response to phorbol esters. Nature. 1987 Oct 15;329(6140):648–651. doi: 10.1038/329648a0. [DOI] [PubMed] [Google Scholar]
  7. Chodosh L. A., Baldwin A. S., Carthew R. W., Sharp P. A. Human CCAAT-binding proteins have heterologous subunits. Cell. 1988 Apr 8;53(1):11–24. doi: 10.1016/0092-8674(88)90483-7. [DOI] [PubMed] [Google Scholar]
  8. Dynan W. S., Tjian R. The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter. Cell. 1983 Nov;35(1):79–87. doi: 10.1016/0092-8674(83)90210-6. [DOI] [PubMed] [Google Scholar]
  9. Feuerstein N., Cooper H. L. Rapid protein phosphorylation induced by phorbol ester in HL-60 cells. Unique alkali-stable phosphorylation of a 17,000-dalton protein detected by two-dimensional gel electrophoresis. J Biol Chem. 1983 Sep 10;258(17):10786–10793. [PubMed] [Google Scholar]
  10. Fujita T., Shibuya H., Ohashi T., Yamanishi K., Taniguchi T. Regulation of human interleukin-2 gene: functional DNA sequences in the 5' flanking region for the gene expression in activated T lymphocytes. Cell. 1986 Aug 1;46(3):401–405. doi: 10.1016/0092-8674(86)90660-4. [DOI] [PubMed] [Google Scholar]
  11. Grosso L. E., Pitot H. C. Transcriptional regulation of c-myc during chemically induced differentiation of HL-60 cultures. Cancer Res. 1985 Feb;45(2):847–850. [PubMed] [Google Scholar]
  12. Halazonetis T. D., Georgopoulos K., Greenberg M. E., Leder P. c-Jun dimerizes with itself and with c-Fos, forming complexes of different DNA binding affinities. Cell. 1988 Dec 2;55(5):917–924. doi: 10.1016/0092-8674(88)90147-x. [DOI] [PubMed] [Google Scholar]
  13. Harris P., Ralph P. Human leukemic models of myelomonocytic development: a review of the HL-60 and U937 cell lines. J Leukoc Biol. 1985 Apr;37(4):407–422. doi: 10.1002/jlb.37.4.407. [DOI] [PubMed] [Google Scholar]
  14. Hata A., Ohno S., Akita Y., Suzuki K. Tandemly reiterated negative enhancer-like elements regulate transcription of a human gene for the large subunit of calcium-dependent protease. J Biol Chem. 1989 Apr 15;264(11):6404–6411. [PubMed] [Google Scholar]
  15. Huberman E., Callaham M. F. Induction of terminal differentiation in human promyelocytic leukemia cells by tumor-promoting agents. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1293–1297. doi: 10.1073/pnas.76.3.1293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jones K. A., Kadonaga J. T., Rosenfeld P. J., Kelly T. J., Tjian R. A cellular DNA-binding protein that activates eukaryotic transcription and DNA replication. Cell. 1987 Jan 16;48(1):79–89. doi: 10.1016/0092-8674(87)90358-8. [DOI] [PubMed] [Google Scholar]
  17. Kageyama R., Pastan I. Molecular cloning and characterization of a human DNA binding factor that represses transcription. Cell. 1989 Dec 1;59(5):815–825. doi: 10.1016/0092-8674(89)90605-3. [DOI] [PubMed] [Google Scholar]
  18. Kitabayashi I., Saka F., Gachelin G., Yokoyama K. Nucleotide sequence of rat c-jun protooncogene. Nucleic Acids Res. 1990 Jun 11;18(11):3400–3400. doi: 10.1093/nar/18.11.3400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kouzarides T., Ziff E. Leucine zippers of fos, jun and GCN4 dictate dimerization specificity and thereby control DNA binding. Nature. 1989 Aug 17;340(6234):568–571. doi: 10.1038/340568a0. [DOI] [PubMed] [Google Scholar]
  20. Kraft A. S., Anderson W. B., Cooper H. L., Sando J. J. Decrease in cytosolic calcium/phospholipid-dependent protein kinase activity following phorbol ester treatment of EL4 thymoma cells. J Biol Chem. 1982 Nov 25;257(22):13193–13196. [PubMed] [Google Scholar]
  21. Kraft A. S., Anderson W. B. Phorbol esters increase the amount of Ca2+, phospholipid-dependent protein kinase associated with plasma membrane. Nature. 1983 Feb 17;301(5901):621–623. doi: 10.1038/301621a0. [DOI] [PubMed] [Google Scholar]
  22. Kraft A. S., Baker V. V., May W. S. Bryostatin induces changes in protein kinase C location and activity without altering c-myc gene expression in human promyelocytic leukemia cells (HL-60). Oncogene. 1987 May;1(2):111–118. [PubMed] [Google Scholar]
  23. König H., Ponta H., Rahmsdorf U., Büscher M., Schönthal A., Rahmsdorf H. J., Herrlich P. Autoregulation of fos: the dyad symmetry element as the major target of repression. EMBO J. 1989 Sep;8(9):2559–2566. doi: 10.1002/j.1460-2075.1989.tb08394.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lee W., Mitchell P., Tjian R. Purified transcription factor AP-1 interacts with TPA-inducible enhancer elements. Cell. 1987 Jun 19;49(6):741–752. doi: 10.1016/0092-8674(87)90612-x. [DOI] [PubMed] [Google Scholar]
  25. Macgregor P. F., Abate C., Curran T. Direct cloning of leucine zipper proteins: Jun binds cooperatively to the CRE with CRE-BP1. Oncogene. 1990 Apr;5(4):451–458. [PubMed] [Google Scholar]
  26. McKnight S., Tjian R. Transcriptional selectivity of viral genes in mammalian cells. Cell. 1986 Sep 12;46(6):795–805. doi: 10.1016/0092-8674(86)90061-9. [DOI] [PubMed] [Google Scholar]
  27. Mita S., Nakaki T., Yamamoto S., Kato R. Phosphorylation and dephosphorylation of human promyelocytic leukemia cell (HL-60) proteins by tumor promoter. Exp Cell Res. 1984 Oct;154(2):492–499. doi: 10.1016/0014-4827(84)90173-3. [DOI] [PubMed] [Google Scholar]
  28. Neuberg M., Schuermann M., Hunter J. B., Müller R. Two functionally different regions in Fos are required for the sequence-specific DNA interaction of the Fos/Jun protein complex. Nature. 1989 Apr 13;338(6216):589–590. doi: 10.1038/338589a0. [DOI] [PubMed] [Google Scholar]
  29. Ransone L. J., Visvader J., Sassone-Corsi P., Verma I. M. Fos-Jun interaction: mutational analysis of the leucine zipper domain of both proteins. Genes Dev. 1989 Jun;3(6):770–781. doi: 10.1101/gad.3.6.770. [DOI] [PubMed] [Google Scholar]
  30. Reitsma P. H., Rothberg P. G., Astrin S. M., Trial J., Bar-Shavit Z., Hall A., Teitelbaum S. L., Kahn A. J. Regulation of myc gene expression in HL-60 leukaemia cells by a vitamin D metabolite. Nature. 1983 Dec 1;306(5942):492–494. doi: 10.1038/306492a0. [DOI] [PubMed] [Google Scholar]
  31. Rovera G., Santoli D., Damsky C. Human promyelocytic leukemia cells in culture differentiate into macrophage-like cells when treated with a phorbol diester. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2779–2783. doi: 10.1073/pnas.76.6.2779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Santoro C., Mermod N., Andrews P. C., Tjian R. A family of human CCAAT-box-binding proteins active in transcription and DNA replication: cloning and expression of multiple cDNAs. Nature. 1988 Jul 21;334(6179):218–224. doi: 10.1038/334218a0. [DOI] [PubMed] [Google Scholar]
  33. Sassone-Corsi P., Ransone L. J., Verma I. M. Cross-talk in signal transduction: TPA-inducible factor jun/AP-1 activates cAMP-responsive enhancer elements. Oncogene. 1990 Mar;5(3):427–431. [PubMed] [Google Scholar]
  34. Westin E. H., Wong-Staal F., Gelmann E. P., Dalla-Favera R., Papas T. S., Lautenberger J. A., Eva A., Reddy E. P., Tronick S. R., Aaronson S. A. Expression of cellular homologues of retroviral onc genes in human hematopoietic cells. Proc Natl Acad Sci U S A. 1982 Apr;79(8):2490–2494. doi: 10.1073/pnas.79.8.2490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. William F., Mroczkowski B., Cohen S., Kraft A. S. Differentiation of HL-60 cells is associated with an increase in the 35-kDa protein lipocortin I. J Cell Physiol. 1988 Dec;137(3):402–410. doi: 10.1002/jcp.1041370303. [DOI] [PubMed] [Google Scholar]
  36. William F., Wagner F., Karin M., Kraft A. S. Multiple doses of diacylglycerol and calcium ionophore are necessary to activate AP-1 enhancer activity and induce markers of macrophage differentiation. J Biol Chem. 1990 Oct 25;265(30):18166–18171. [PubMed] [Google Scholar]
  37. de Groot R. P., Pals C., Kruijer W. Transcriptional control of c-jun by retinoic acid. Nucleic Acids Res. 1991 Apr 11;19(7):1585–1591. doi: 10.1093/nar/19.7.1585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. van Dam H., Offringa R., Meijer I., Stein B., Smits A. M., Herrlich P., Bos J. L., van der Eb A. J. Differential effects of the adenovirus E1A oncogene on members of the AP-1 transcription factor family. Mol Cell Biol. 1990 Nov;10(11):5857–5864. doi: 10.1128/mcb.10.11.5857. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES