Immediate-early genes and opioid peptides

  • J. Kraus
  • B. Bacher
  • X. Wang
  • V. Höllt


Cellular stimulation causes the rapid appearance of proteins in the nucleus which function as signal-regulated transcription factors converting membrane events into long-term changes in gene expression. These transcription factors are the products of a variety of immediate early genes (IEG). One important group of these signal- regulated transcription factors are the BZip proteins which contain each a basic (B) and a leucine zipper (Zip) domain that are required for DNA binding and dimerization, respectively.


Bovine Chromaffin Cell POMC Gene Bovine Adrenal Medullary Cell Prodynorphin Gene POMC Gene Expression 
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  1. Angel P, Imagawa M, Chiu R, Stein B, Imbra RJ, Rahmsdorf HJ, Jonat C, Herrlich P, Karin M (1987) Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell 49:729–739PubMedCrossRefGoogle Scholar
  2. Berkowitz LA, Riabowol KT, Gilman MZ (1989) Multiple sequence elements of a single functional class are required for cyclic AMP responsiveness of the mouse c-fos promoter. Mol Cell Biol 9:4272–4281PubMedGoogle Scholar
  3. Bishop JF, Rinaudo MS, Ritter JK, Chang AC, Conant K, Gehlert DR (1990) A putative AP-2 binding site in the 5′ flanking region of the mouse POMC gene. FEBS Lett 264:125–129PubMedCrossRefGoogle Scholar
  4. Boutillier AL, Sassone Corsi P, Loeffler JP (1991) The protooncogene c-fos is induced by corticotropin-releasing factor and stimulates proopiomelanocortin gene transcription in pituitary cells. Mol Endocrinol 5:1301–1310PubMedCrossRefGoogle Scholar
  5. Boutillier AL, Barthel F, Roberts JL, Loeffler JP (1992) Beta-adrenergic stimulation of c-Fos via protein kinase A is mediated by cAMP regulatory element binding protein (CREB)-dependent and tissue-specific CREB-independent mechanisms in corticotrope cells. J Biol Chem 267:23520–23526PubMedGoogle Scholar
  6. Chiu R, Boyle WJ, Meek J, Smeal T, Hunter T, Karin M (1988) The c-Fos protein interacts with c-Jun/AP-1 to stimulate transcription of AP-1 responsive genes. Cell 54:541–552PubMedCrossRefGoogle Scholar
  7. Comb M, Birnberg NC, Seasholtz A, Herbert E, Goodman HM (1986) A cyclic AMP- and phorbol ester-inducible DNA element. Nature 323:353–356PubMedCrossRefGoogle Scholar
  8. Comb M, Mermod N, Hyman SE, Pearlberg J, Ross ME, Goodman HM (1988) Proteins bound at adjacent DNA elements act synergistically to regulate human proenkephalin cAMP inducible transcription. EMBO J 7:3793–3805PubMedGoogle Scholar
  9. Deutsch PJ, Hoeffler JP, Jameson JL, Lin JC, Habener JF (1988) Structural determinants for transcriptional activation by cAMP-responsive DNA elements. J Biol Chem 263:18466–18472PubMedGoogle Scholar
  10. Drouin J, Nemer M, Charron J, Gagner JP, Jeannotte L, Sun YL, Therrien M, Tremblay Y (1989) Tissue-specific activity of the pro-opiomelanocortin (POMC) gene and repression by glucocorticoids. Genome 31:510–519PubMedCrossRefGoogle Scholar
  11. Edelman AM, Blumenthal DK, Krebs EG (1987) Protein serine/threonine kinases. Annu Rev Biochem 56:567–613PubMedCrossRefGoogle Scholar
  12. Farin CJ, Kley N, Hollt V. (1990) Mechanisms involved in the transcriptional activation of proenkephalin gene expression in bovine chromaffin cells. J Biol Chem 265:19116–19121PubMedGoogle Scholar
  13. Fink JS, Verhave M, Walton K, Mandel G, Goodman RH (1991) Cyclic AMP- and phorbol ester-induced transcriptional activation are mediated by the same enhancer element in the human vasoactive intestinal peptide gene. J Biol Chem 266:3882–3887PubMedGoogle Scholar
  14. Gonzalez GA, Montminy MR (1989) Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell 59:675–680PubMedCrossRefGoogle Scholar
  15. Hai T, Curran T (1991) Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity. Proc Natl Acad Sci USA 88:3720–3724PubMedCrossRefGoogle Scholar
  16. Hai TW, Liu F, Coukos WJ, Green MR (1989) Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers [published erratum appears in Genes Dev 1990 Apr;4(4):682]. Genes Dev 3:2083–2090PubMedCrossRefGoogle Scholar
  17. Hoeffler JP, Meyer TE, Waeber G, Habener JF (1990) Multiple adenosine 3′\5′-cyclic [corrected] monophosphate response element DNA-binding proteins generated by gene diversification and alternative exon splicing [published erratum appears in Mol Endocrinol 1990 Jul;4(7): 1016]. Mol Endocrinol 4:920–930PubMedCrossRefGoogle Scholar
  18. Hollt V (1983) Multiple endogenous opioid peptides. Trends Neurosci 6:24–26CrossRefGoogle Scholar
  19. Hollt V (1993) Regulation of opioid peptide gene expression. In: Herz A (ed) Handbook of experimental pharmacology, Vol104/I Opioids I., Springer Verlag, Berlin, pp 307–364Google Scholar
  20. Hollt V, Haarmann I, Millan MJ, Herz A (1987) Prodynorphin gene expression is enhanced in the spinal cord of chronic arthritic rats. Neurosci Lett 73:90–94PubMedCrossRefGoogle Scholar
  21. Huggenvik JI, Collard MW, Stofko RE, Seasholtz AF, Uhler MD (1991) Regulation of the human enkephalin promoter by two isoforms of the catalytic subunit of cyclic adenosine 3′,5′- monophosphate-dependent protein kinase. Mol Endocrinol 5:921–930PubMedCrossRefGoogle Scholar
  22. Hyman SE, Comb M, Pearlberg J, Goodman HM (1989) An AP-2 element acts synergistically with the cyclic AMP- and phorbol ester-inducible enhancer of the human proenkephalin gene. Mol Cell Biol 9:321–324PubMedGoogle Scholar
  23. Iadarola MJ, Douglass J, Civelli O, Naranjo JR (1988) Differential activation of spinal cord dynorphin and enkephalin neurons during hyperalgesia: evidence using cDNA hybridization. Brain Res 455:205–212PubMedCrossRefGoogle Scholar
  24. Jeannotte L, Trifiro MA, Plante RK, Chamberland M, Drouin J (1987) Tissue-specific activity of the pro-opiomelanocortin gene promoter. Mol Cell Biol 7:4058–4064PubMedGoogle Scholar
  25. Karin M (1989) Complexities of gene regulation by cAMP. Trends Genet 5: 65–67PubMedCrossRefGoogle Scholar
  26. Karin M, Smeal T (1992) Control of transcription factors by signal transduction pathways: the beginning of the end. Trends Biochem Sci 17: 418–422PubMedCrossRefGoogle Scholar
  27. Kobierski LA, Chu HM, Tan Y, Comb MJ (1991) cAMP-dependent regulation of proenkephalin by Jun D and Jun B: positive and negative effects of AP-1 proteins. Proc Natl Acad Sci USA 88:10222–10226PubMedCrossRefGoogle Scholar
  28. Konradi C, Kobierski LA, Nguyen TV, Heckers S, Hyman SE (1993) The cAMP-response-element-binding protein interacts, but Fos protein does not interact, with the proenkephalin enhancer in rat striatum. Proc Natl Acad Sci USA 9:7005–7009CrossRefGoogle Scholar
  29. Kraus J, Buchfelder M, Hollt V (1993) Regulatory elements of the human proopiomelanocortin gene promoter. DNA Cell Biol 12:527–536PubMedCrossRefGoogle Scholar
  30. Kraus J, Hollt V (1993) Identification of hormone response elements of the human proopiomelanocortin gene promoter. Eur J Physiol 422:Suppl 1, R87. (Abstract)Google Scholar
  31. Liu B, Hammer GD, Rubinstein M, Mortrud M, Low MJ (1992) Identification of DNA elements cooperatively activating proopiomelanocortin gene expression in the pituitary glands of transgenic mice. Mol Cell Biol 12: 3978–3990PubMedGoogle Scholar
  32. Loeffler JP, Kley N, Pittius CW, Hollt V (1986) Calcium ion and cyclic adenosine 3′,5′- monophosphate regulate proopiomelanocortin messenger ribonucleic acid levels in rat intermediate and anterior pituitary lobes. Endocrinology 119:2840–2847PubMedCrossRefGoogle Scholar
  33. Lucas JJ, Mellstrom B, Colado MI, Naranjo JR (1993) Molecular mechanisms of pain: serotonin 1A receptor agonists trigger transactivation by c-fos of the prodynorphin gene in spinal cord neurons. Neuron 10:599–611PubMedCrossRefGoogle Scholar
  34. Masquilier D, Sassone Corsi P (1992) Transcriptional cross-talk: nuclear factors CREM and CREB bind to AP-1 sites and inhibit activation by Jun. J Biol Chem 267:22460–22466PubMedGoogle Scholar
  35. McMurray CT, Devi L, Calavetta L, Douglass JO (1989) Regulated expression of the prodynorphin gene in the R2C Leydig tumor cell line. Endocrinology 124:49–59PubMedCrossRefGoogle Scholar
  36. Montminy MR, Sevarino KA, Wagner JA, Mandel G, Goodman RH (1986) Identification of a cyclic-AMP-responsive element within the rat somatostatin gene. Proc Natl Acad Sci USA 83:6682–6686PubMedCrossRefGoogle Scholar
  37. Montminy MR, Bilezikjian LM (1987) Binding of a nuclear protein to the cyclic-AMP response element of the somatostatin gene. Nature 328:175–178PubMedCrossRefGoogle Scholar
  38. Morgan JI, Curran T (1991) Stimulus-transcription coupling in the nervous system: involvement of the inducible proto-oncogenes fos and jun. Annu Rev Neurosci 14:421–451PubMedCrossRefGoogle Scholar
  39. Naranjo JR, Mellstrom B, Achaval M, Sassone Corsi P (1991) Molecular pathways of pain: Fos/Jun-mediated activation of a noncanonical AP-1 site in the prodynorphin gene. Neuron 6:607–617PubMedCrossRefGoogle Scholar
  40. Nishimori T, Buzzi MG, Moskowitz MA, Uhl GR (1989) Preproenkephalin mRNA expression in nucleus caudalis neurons is enhanced by trigeminal stimulation. Brain Res Mol Brain Res 6:203–210PubMedCrossRefGoogle Scholar
  41. Noguchi K, Kowalski K, Traub R, Solodkin A, Iadarola MJ, Ruda MA (1991) Dynorphin expression and Fos-like immunoreactivity following inflammation induced hyperalgesia are colocalized in spinal cord neurons. Brain Res Mol Brain Res 10:227–233PubMedCrossRefGoogle Scholar
  42. Rauscher FJ, Voulalas PJ, Franza BRJ, Curran T (1988) Fos and Jun bind cooperatively to the AP-1 site: reconstitution in vitro. Genes Dev 2:1687–1699PubMedCrossRefGoogle Scholar
  43. Reisine T, Rougon G, Barbet J, Affolter HU (1985) Corticotropin-releasing factor-induced adrenocorticotropin hormone release and synthesis is blocked by incorporation of the inhibitor of cyclic AMP-dependent protein kinase into anterior pituitary tumor cells by liposomes. Proc Natl Acad Sci USA 82:8261–8265PubMedCrossRefGoogle Scholar
  44. Riegel AT, Remenick J, Wolford RG, Berard DS, Hager GL (1990) A novel transcriptional activator (PO-B) binds between the TATA box and cap site of the pro-opiomelanocortin gene. Nucleic Acids Res 18:4513–4521PubMedCrossRefGoogle Scholar
  45. Roberts JL, Lundblad JR, Eberwine JH, Fremeau RT, Salton SR, Blum M (1987) Hormonal regulation of POMC gene expression in pituitary. Ann N Y Acad Sci 512:275–285PubMedCrossRefGoogle Scholar
  46. Ruppert S, Cole TJ, Boshart M, Schmid E, Schutz G (1992) Multiple mRNA isoforms of the transcription activator protein CREB: generation by alternative splicing and specific expression in primary spermatocytes. EMBO J 11:1503–1512PubMedGoogle Scholar
  47. Sonnenberg JL, Rauscher FJ, Morgan JI, Curran T (1989) Regulation of proenkephalin by Fos and Jun. Science 246:1622–1625PubMedCrossRefGoogle Scholar
  48. Stachowiak MK, Hong JS, Viveros OH (1990) Coordinate and differential regulation of phenylethanolamine N-methyltransferase, tyrosine hydroxylase and proenkephalin mRNAs by neural and hormonal mechanisms in cultured bovine adrenal medullary cells. Brain Res 510: 277–288PubMedCrossRefGoogle Scholar
  49. Sukhatme VP, Cao XM, Chang LC, Tsai Morris CH, Stamenkovich D, Ferreira PC, Cohen DR, Edwards SA, Shows TB, Curran T et al (1988) A zinc finger-encoding gene coregulated with c-fos during growth and differentiation, and after cellular depolarization. Cell 53:37–43PubMedCrossRefGoogle Scholar
  50. Therrien M, Drouin J (1991) Pituitary pro-opiomelanocortin gene expression requires synergistic interactions of several regulatory elements. Mol Cell Biol 11:3492–3503PubMedGoogle Scholar
  51. Therrien M, Drouin J (1993) Cell-specific helix-loop-helix factor required for pituitary expression of the pro-opiomelanocortin gene. Mol Cell Biol 13:2342–2353PubMedGoogle Scholar
  52. Tremblay Y, Tretjakoff I, Peterson A, Antakly T, Zhang CX, Drouin J (1988) Pituitary-specific expression and glucocorticoid regulation of a proopiomelanocortin fusion gene in transgenic mice. Proc Natl Acad Sci USA 85:8890–8894PubMedCrossRefGoogle Scholar
  53. Usui T, Nakai Y, Tsukada T, Fukata J, Nakaishi S, Naitoh Y, Imura H (1989) Cyclic AMP- responsive region of the human proopiomelanocortin (POMC) gene. Mol Cell Endocrinol 62:141–146PubMedCrossRefGoogle Scholar
  54. Van Nguyen T, Kobierski L, Comb M, Hyman SE (1990) The effect of depolarization on expression of the human proenkephalin gene is synergistic with cAMP and dependent upon a cAMP-inducible enhancer. J Neurosci 10:2825–2833PubMedGoogle Scholar
  55. Wang X, Bacher B, Hollt V (1993) Gene expression in bovine adrenal chromaffin cells: relationship between c-Fos/c-Jun and proenkephalin. Eur J Physiol 422, Suppl 1, R92. (Abstract)Google Scholar
  56. Wellstein A, Dobrenski AF, Radonovich MN, Brady JF, Riegel AT (1991) Purification of PO-B, a protein that has increased affinity for the pro-opiomelanocortin gene promoter after dephosphorylation. J Biol Chem 266:12234–12241PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • J. Kraus
    • 1
  • B. Bacher
    • 1
  • X. Wang
    • 1
  • V. Höllt
    • 1
  1. 1.Institute of PhysiologyUniversity of MunichMünchenGermany

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