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. 1991 Feb 25;19(4):775–781. doi: 10.1093/nar/19.4.775

Activation of junB by PKC and PKA signal transduction through a novel cis-acting element.

R P de Groot 1, J Auwerx 1, M Karperien 1, B Staels 1, W Kruijer 1
PMCID: PMC333710  PMID: 1708123

Abstract

The product of the junB gene, a gene homologous to the proto-oncogene c-jun, is a component of transcription factor AP-1. JunB expression is modulated by a wide variety of extracellular stimuli, such as serum, growth factors, phorbol esters (TPA) and activators of protein kinase A (PKA). In order to study the molecular basis of this complex regulation, we have cloned the mouse junB gene from a genomic testis library, and characterized the junB promoter. Here we show that the junB promoter is activated by serum, TPA, and activated PKA. Sequences located between -91 and -44 are necessary for induction. These sequences contain a CAAT box, a G-C rich region and a previously undescribed inverted repeat (IR). The IR element can mediate induction by TPA and PKA when coupled to a heterologous promoter, and specifically binds a protein of 110 kD.

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Selected References

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  1. Angel P., Allegretto E. A., Okino S. T., Hattori K., Boyle W. J., Hunter T., Karin M. Oncogene jun encodes a sequence-specific trans-activator similar to AP-1. Nature. 1988 Mar 10;332(6160):166–171. doi: 10.1038/332166a0. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. Auwerx J., Staels B., Sassone-Corsi P. Coupled and uncoupled induction of fos and jun transcription by different second messengers in cells of hematopoietic origin. Nucleic Acids Res. 1990 Jan 25;18(2):221–228. doi: 10.1093/nar/18.2.221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bartel D. P., Sheng M., Lau L. F., Greenberg M. E. Growth factors and membrane depolarization activate distinct programs of early response gene expression: dissociation of fos and jun induction. Genes Dev. 1989 Mar;3(3):304–313. doi: 10.1101/gad.3.3.304. [DOI] [PubMed] [Google Scholar]
  6. Bohmann D., Bos T. J., Admon A., Nishimura T., Vogt P. K., Tjian R. Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1. Science. 1987 Dec 4;238(4832):1386–1392. doi: 10.1126/science.2825349. [DOI] [PubMed] [Google Scholar]
  7. Boshart M., Weih F., Schmidt A., Fournier R. E., Schütz G. A cyclic AMP response element mediates repression of tyrosine aminotransferase gene transcription by the tissue-specific extinguisher locus Tse-1. Cell. 1990 Jun 1;61(5):905–916. doi: 10.1016/0092-8674(90)90201-o. [DOI] [PubMed] [Google Scholar]
  8. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  9. Chiu R., Angel P., Karin M. Jun-B differs in its biological properties from, and is a negative regulator of, c-Jun. Cell. 1989 Dec 22;59(6):979–986. doi: 10.1016/0092-8674(89)90754-x. [DOI] [PubMed] [Google Scholar]
  10. Chiu R., Boyle W. J., Meek J., Smeal T., Hunter T., Karin M. The c-Fos protein interacts with c-Jun/AP-1 to stimulate transcription of AP-1 responsive genes. Cell. 1988 Aug 12;54(4):541–552. doi: 10.1016/0092-8674(88)90076-1. [DOI] [PubMed] [Google Scholar]
  11. Christy B., Nathans D. DNA binding site of the growth factor-inducible protein Zif268. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8737–8741. doi: 10.1073/pnas.86.22.8737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cleveland D. W., Lopata M. A., MacDonald R. J., Cowan N. J., Rutter W. J., Kirschner M. W. Number and evolutionary conservation of alpha- and beta-tubulin and cytoplasmic beta- and gamma-actin genes using specific cloned cDNA probes. Cell. 1980 May;20(1):95–105. doi: 10.1016/0092-8674(80)90238-x. [DOI] [PubMed] [Google Scholar]
  13. Cohen D. R., Curran T. fra-1: a serum-inducible, cellular immediate-early gene that encodes a fos-related antigen. Mol Cell Biol. 1988 May;8(5):2063–2069. doi: 10.1128/mcb.8.5.2063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Curran T., Franza B. R., Jr Fos and Jun: the AP-1 connection. Cell. 1988 Nov 4;55(3):395–397. doi: 10.1016/0092-8674(88)90024-4. [DOI] [PubMed] [Google Scholar]
  15. Fort P., Marty L., Piechaczyk M., el Sabrouty S., Dani C., Jeanteur P., Blanchard J. M. Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. Nucleic Acids Res. 1985 Mar 11;13(5):1431–1442. doi: 10.1093/nar/13.5.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gonzalez G. A., Montminy M. R. Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell. 1989 Nov 17;59(4):675–680. doi: 10.1016/0092-8674(89)90013-5. [DOI] [PubMed] [Google Scholar]
  17. Gonzalez G. A., Yamamoto K. K., Fischer W. H., Karr D., Menzel P., Biggs W., 3rd, Vale W. W., Montminy M. R. A cluster of phosphorylation sites on the cyclic AMP-regulated nuclear factor CREB predicted by its sequence. Nature. 1989 Feb 23;337(6209):749–752. doi: 10.1038/337749a0. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Hai T. W., Liu F., Coukos W. J., Green M. R. Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers. Genes Dev. 1989 Dec;3(12B):2083–2090. doi: 10.1101/gad.3.12b.2083. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Hattori K., Angel P., Le Beau M. M., Karin M. Structure and chromosomal localization of the functional intronless human JUN protooncogene. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9148–9152. doi: 10.1073/pnas.85.23.9148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hoeffler J. P., Meyer T. E., Yun Y., Jameson J. L., Habener J. F. Cyclic AMP-responsive DNA-binding protein: structure based on a cloned placental cDNA. Science. 1988 Dec 9;242(4884):1430–1433. doi: 10.1126/science.2974179. [DOI] [PubMed] [Google Scholar]
  23. Imler J. L., Wasylyk B. AP1, a composite transcription factor implicated in abnormal growth control. Prog Growth Factor Res. 1989;1(2):69–77. doi: 10.1016/0955-2235(89)90001-x. [DOI] [PubMed] [Google Scholar]
  24. Jones K. A., Yamamoto K. R., Tjian R. Two distinct transcription factors bind to the HSV thymidine kinase promoter in vitro. Cell. 1985 Sep;42(2):559–572. doi: 10.1016/0092-8674(85)90113-8. [DOI] [PubMed] [Google Scholar]
  25. Karin M. Complexities of gene regulation by cAMP. Trends Genet. 1989 Mar;5(3):65–67. doi: 10.1016/0168-9525(89)90027-9. [DOI] [PubMed] [Google Scholar]
  26. Lamph W. W., Dwarki V. J., Ofir R., Montminy M., Verma I. M. Negative and positive regulation by transcription factor cAMP response element-binding protein is modulated by phosphorylation. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4320–4324. doi: 10.1073/pnas.87.11.4320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lamph W. W., Wamsley P., Sassone-Corsi P., Verma I. M. Induction of proto-oncogene JUN/AP-1 by serum and TPA. Nature. 1988 Aug 18;334(6183):629–631. doi: 10.1038/334629a0. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Maekawa T., Sakura H., Kanei-Ishii C., Sudo T., Yoshimura T., Fujisawa J., Yoshida M., Ishii S. Leucine zipper structure of the protein CRE-BP1 binding to the cyclic AMP response element in brain. EMBO J. 1989 Jul;8(7):2023–2028. doi: 10.1002/j.1460-2075.1989.tb03610.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Maki Y., Bos T. J., Davis C., Starbuck M., Vogt P. K. Avian sarcoma virus 17 carries the jun oncogene. Proc Natl Acad Sci U S A. 1987 May;84(9):2848–2852. doi: 10.1073/pnas.84.9.2848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. McBurney M. W., Jones-Villeneuve E. M., Edwards M. K., Anderson P. J. Control of muscle and neuronal differentiation in a cultured embryonal carcinoma cell line. Nature. 1982 Sep 9;299(5879):165–167. doi: 10.1038/299165a0. [DOI] [PubMed] [Google Scholar]
  32. Mechta F., Piette J., Hirai S. I., Yaniv M. Stimulation of protein kinase C or protein kinase A mediated signal transduction pathways shows three modes of response among serum inducible genes. New Biol. 1989 Dec;1(3):297–304. [PubMed] [Google Scholar]
  33. Mitchell P. J., Tjian R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science. 1989 Jul 28;245(4916):371–378. doi: 10.1126/science.2667136. [DOI] [PubMed] [Google Scholar]
  34. Montminy M. R., Bilezikjian L. M. Binding of a nuclear protein to the cyclic-AMP response element of the somatostatin gene. Nature. 1987 Jul 9;328(6126):175–178. doi: 10.1038/328175a0. [DOI] [PubMed] [Google Scholar]
  35. Nishina H., Sato H., Suzuki T., Sato M., Iba H. Isolation and characterization of fra-2, an additional member of the fos gene family. Proc Natl Acad Sci U S A. 1990 May;87(9):3619–3623. doi: 10.1073/pnas.87.9.3619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Nishizuka Y. Studies and perspectives of protein kinase C. Science. 1986 Jul 18;233(4761):305–312. doi: 10.1126/science.3014651. [DOI] [PubMed] [Google Scholar]
  37. Orellana S. A., McKnight G. S. The S49 Kin- cell line transcribes and translates a functional mRNA coding for the catalytic subunit of cAMP-dependent protein kinase. J Biol Chem. 1990 Feb 25;265(6):3048–3053. [PubMed] [Google Scholar]
  38. Quantin B., Breathnach R. Epidermal growth factor stimulates transcription of the c-jun proto-oncogene in rat fibroblasts. Nature. 1988 Aug 11;334(6182):538–539. doi: 10.1038/334538a0. [DOI] [PubMed] [Google Scholar]
  39. Rauscher F. J., 3rd, Cohen D. R., Curran T., Bos T. J., Vogt P. K., Bohmann D., Tjian R., Franza B. R., Jr Fos-associated protein p39 is the product of the jun proto-oncogene. Science. 1988 May 20;240(4855):1010–1016. doi: 10.1126/science.3130660. [DOI] [PubMed] [Google Scholar]
  40. Rauscher F. J., 3rd, Voulalas P. J., Franza B. R., Jr, Curran T. Fos and Jun bind cooperatively to the AP-1 site: reconstitution in vitro. Genes Dev. 1988 Dec;2(12B):1687–1699. doi: 10.1101/gad.2.12b.1687. [DOI] [PubMed] [Google Scholar]
  41. Roesler W. J., Vandenbark G. R., Hanson R. W. Cyclic AMP and the induction of eukaryotic gene transcription. J Biol Chem. 1988 Jul 5;263(19):9063–9066. [PubMed] [Google Scholar]
  42. Ryder K., Lanahan A., Perez-Albuerne E., Nathans D. jun-D: a third member of the jun gene family. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1500–1503. doi: 10.1073/pnas.86.5.1500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Ryder K., Lau L. F., Nathans D. A gene activated by growth factors is related to the oncogene v-jun. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1487–1491. doi: 10.1073/pnas.85.5.1487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Ryseck R. P., Hirai S. I., Yaniv M., Bravo R. Transcriptional activation of c-jun during the G0/G1 transition in mouse fibroblasts. Nature. 1988 Aug 11;334(6182):535–537. doi: 10.1038/334535a0. [DOI] [PubMed] [Google Scholar]
  45. Sassone-Corsi P., Lamph W. W., Kamps M., Verma I. M. fos-associated cellular p39 is related to nuclear transcription factor AP-1. Cell. 1988 Aug 12;54(4):553–560. doi: 10.1016/0092-8674(88)90077-3. [DOI] [PubMed] [Google Scholar]
  46. Schütte J., Viallet J., Nau M., Segal S., Fedorko J., Minna J. jun-B inhibits and c-fos stimulates the transforming and trans-activating activities of c-jun. Cell. 1989 Dec 22;59(6):987–997. doi: 10.1016/0092-8674(89)90755-1. [DOI] [PubMed] [Google Scholar]
  47. Smeal T., Angel P., Meek J., Karin M. Different requirements for formation of Jun: Jun and Jun: Fos complexes. Genes Dev. 1989 Dec;3(12B):2091–2100. doi: 10.1101/gad.3.12b.2091. [DOI] [PubMed] [Google Scholar]
  48. Szpirer C., Szpirer J. A mouse hepatoma cell line which secretes several serum proteins including albumin and alpha-foetoprotein. Differentiation. 1975 Oct 16;4(2):85–91. doi: 10.1111/j.1432-0436.1975.tb01446.x. [DOI] [PubMed] [Google Scholar]
  49. Treisman R. Identification and purification of a polypeptide that binds to the c-fos serum response element. EMBO J. 1987 Sep;6(9):2711–2717. doi: 10.1002/j.1460-2075.1987.tb02564.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Treisman R. Identification of a protein-binding site that mediates transcriptional response of the c-fos gene to serum factors. Cell. 1986 Aug 15;46(4):567–574. doi: 10.1016/0092-8674(86)90882-2. [DOI] [PubMed] [Google Scholar]
  51. Vogt P. K., Bos T. J., Doolittle R. F. Homology between the DNA-binding domain of the GCN4 regulatory protein of yeast and the carboxyl-terminal region of a protein coded for by the oncogene jun. Proc Natl Acad Sci U S A. 1987 May;84(10):3316–3319. doi: 10.1073/pnas.84.10.3316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Vogt P. K., Bos T. J. The oncogene jun and nuclear signalling. Trends Biochem Sci. 1989 May;14(5):172–175. doi: 10.1016/0968-0004(89)90268-5. [DOI] [PubMed] [Google Scholar]
  53. Yamamoto K. K., Gonzalez G. A., Biggs W. H., 3rd, Montminy M. R. Phosphorylation-induced binding and transcriptional efficacy of nuclear factor CREB. Nature. 1988 Aug 11;334(6182):494–498. doi: 10.1038/334494a0. [DOI] [PubMed] [Google Scholar]
  54. Zerial M., Toschi L., Ryseck R. P., Schuermann M., Müller R., Bravo R. The product of a novel growth factor activated gene, fos B, interacts with JUN proteins enhancing their DNA binding activity. EMBO J. 1989 Mar;8(3):805–813. doi: 10.1002/j.1460-2075.1989.tb03441.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. de Groot R. P., Kruijer W. Transcriptional activation by TGF beta 1 mediated by the dyad symmetry element (DSE) and the TPA responsive element (TRE). Biochem Biophys Res Commun. 1990 May 16;168(3):1074–1081. doi: 10.1016/0006-291x(90)91139-j. [DOI] [PubMed] [Google Scholar]
  56. de Groot R. P., Kruyt F. A., van der Saag P. T., Kruijer W. Ectopic expression of c-jun leads to differentiation of P19 embryonal carcinoma cells. EMBO J. 1990 Jun;9(6):1831–1837. doi: 10.1002/j.1460-2075.1990.tb08308.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. de Groot R. P., Schoorlemmer J., van Genesen S. T., Kruijer W. Differential expression of jun and fos genes during differentiation of mouse P19 embryonal carcinoma cells. Nucleic Acids Res. 1990 Jun 11;18(11):3195–3202. doi: 10.1093/nar/18.11.3195. [DOI] [PMC free article] [PubMed] [Google Scholar]

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