Skip to main content
PMC home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1997 Feb 15;25(4):877–882. doi: 10.1093/nar/25.4.877

Phosphorylation of ATF-1 enhances its DNA binding and transcription of the Na,K-ATPase alpha 1 subunit gene promoter.

M Kobayashi 1, A Shimomura 1, M Hagiwara 1, K Kawakami 1
PMCID: PMC146500  PMID: 9016641

Abstract

Transcriptional activity of both ATF-1 and CREB is enhanced by protein phosphorylation. While enhancement has been attributed to an increase in binding affinity for a co-activator (CBP), induction of the DNA binding activity by phosphorylation is an open question. Using the Na,K-ATPase alpha1 subunit gene promoter, which has an asymmetrical ATF/CRE site, we analyzed the effect of phosphorylation on DNA binding activity of the ATF-1-CREB heterodimer. Dephosphorylation of the heterodimer in nuclear extracts reduced binding to the ATF/CRE site. Phosphorylation of ATF-1 at Ser63 enhanced its binding to the ATF/CRE site in both the homodimeric and heterodimeric forms. Transcription of the Na,K-ATPase alpha 1 subunit gene promoter was also stimulated by phosphorylated ATF-1 in vitro.

Full Text

The Full Text of this article is available as a PDF (145.1 KB).

Selected References

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

  1. Ahmad M., Medford R. M. Evidence for the regulation of Na+, K(+)-ATPase alpha 1 gene expression through the interaction of aldosterone and cAMP-inducible transcriptional factors. Steroids. 1995 Jan;60(1):147–152. doi: 10.1016/0039-128x(94)00019-9. [DOI] [PubMed] [Google Scholar]
  2. Andrisani O. M., Pot D. A., Zhu Z., Dixon J. E. Three sequence-specific DNA-protein complexes are formed with the same promoter element essential for expression of the rat somatostatin gene. Mol Cell Biol. 1988 May;8(5):1947–1956. doi: 10.1128/mcb.8.5.1947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chrivia J. C., Kwok R. P., Lamb N., Hagiwara M., Montminy M. R., Goodman R. H. Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature. 1993 Oct 28;365(6449):855–859. doi: 10.1038/365855a0. [DOI] [PubMed] [Google Scholar]
  4. Dash P. K., Karl K. A., Colicos M. A., Prywes R., Kandel E. R. cAMP response element-binding protein is activated by Ca2+/calmodulin- as well as cAMP-dependent protein kinase. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):5061–5065. doi: 10.1073/pnas.88.11.5061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Du H., Roy A. L., Roeder R. G. Human transcription factor USF stimulates transcription through the initiator elements of the HIV-1 and the Ad-ML promoters. EMBO J. 1993 Feb;12(2):501–511. doi: 10.1002/j.1460-2075.1993.tb05682.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fujisawa J., Toita M., Yoshida M. A unique enhancer element for the trans activator (p40tax) of human T-cell leukemia virus type I that is distinct from cyclic AMP- and 12-O-tetradecanoylphorbol-13-acetate-responsive elements. J Virol. 1989 Aug;63(8):3234–3239. doi: 10.1128/jvi.63.8.3234-3239.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Giam C. Z., Xu Y. L. HTLV-I tax gene product activates transcription via pre-existing cellular factors and cAMP responsive element. J Biol Chem. 1989 Sep 15;264(26):15236–15241. [PubMed] [Google Scholar]
  8. 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]
  9. Hagiwara M., Alberts A., Brindle P., Meinkoth J., Feramisco J., Deng T., Karin M., Shenolikar S., Montminy M. Transcriptional attenuation following cAMP induction requires PP-1-mediated dephosphorylation of CREB. Cell. 1992 Jul 10;70(1):105–113. doi: 10.1016/0092-8674(92)90537-m. [DOI] [PubMed] [Google Scholar]
  10. Hagiwara M., Brindle P., Harootunian A., Armstrong R., Rivier J., Vale W., Tsien R., Montminy M. R. Coupling of hormonal stimulation and transcription via the cyclic AMP-responsive factor CREB is rate limited by nuclear entry of protein kinase A. Mol Cell Biol. 1993 Aug;13(8):4852–4859. doi: 10.1128/mcb.13.8.4852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hurst H. C., Masson N., Jones N. C., Lee K. A. The cellular transcription factor CREB corresponds to activating transcription factor 47 (ATF-47) and forms complexes with a group of polypeptides related to ATF-43. Mol Cell Biol. 1990 Dec;10(12):6192–6203. doi: 10.1128/mcb.10.12.6192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hurst H. C., Totty N. F., Jones N. C. Identification and functional characterisation of the cellular activating transcription factor 43 (ATF-43) protein. Nucleic Acids Res. 1991 Sep 11;19(17):4601–4609. doi: 10.1093/nar/19.17.4601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kawakami K., Scheidereit C., Roeder R. G. Identification and purification of a human immunoglobulin-enhancer-binding protein (NF-kappa B) that activates transcription from a human immunodeficiency virus type 1 promoter in vitro. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4700–4704. doi: 10.1073/pnas.85.13.4700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kobayashi M., Kawakami K. ATF-1CREB heterodimer is involved in constitutive expression of the housekeeping Na,K-ATPase alpha 1 subunit gene. Nucleic Acids Res. 1995 Aug 11;23(15):2848–2855. doi: 10.1093/nar/23.15.2848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kramer I. M., Koornneef I., de Laat S. W., van den Eijnden-van Raaij A. J. TGF-beta 1 induces phosphorylation of the cyclic AMP responsive element binding protein in ML-CCl64 cells. EMBO J. 1991 May;10(5):1083–1089. doi: 10.1002/j.1460-2075.1991.tb08048.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kwok R. P., Lundblad J. R., Chrivia J. C., Richards J. P., Bächinger H. P., Brennan R. G., Roberts S. G., Green M. R., Goodman R. H. Nuclear protein CBP is a coactivator for the transcription factor CREB. Nature. 1994 Jul 21;370(6486):223–226. doi: 10.1038/370223a0. [DOI] [PubMed] [Google Scholar]
  17. Lee K. A., Green M. R. A cellular transcription factor E4F1 interacts with an E1a-inducible enhancer and mediates constitutive enhancer function in vitro. EMBO J. 1987 May;6(5):1345–1353. doi: 10.1002/j.1460-2075.1987.tb02374.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lee K. A., Masson N. Transcriptional regulation by CREB and its relatives. Biochim Biophys Acta. 1993 Sep 23;1174(3):221–233. doi: 10.1016/0167-4781(93)90191-f. [DOI] [PubMed] [Google Scholar]
  19. Liu F., Thompson M. A., Wagner S., Greenberg M. E., Green M. R. Activating transcription factor-1 can mediate Ca(2+)- and cAMP-inducible transcriptional activation. J Biol Chem. 1993 Mar 25;268(9):6714–6720. [PubMed] [Google Scholar]
  20. Masson N., John J., Lee K. A. In vitro phosphorylation studies of a conserved region of the transcription factor ATF1. Nucleic Acids Res. 1993 Sep 11;21(18):4166–4173. doi: 10.1093/nar/21.18.4166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Matthews R. P., Guthrie C. R., Wailes L. M., Zhao X., Means A. R., McKnight G. S. Calcium/calmodulin-dependent protein kinase types II and IV differentially regulate CREB-dependent gene expression. Mol Cell Biol. 1994 Sep;14(9):6107–6116. doi: 10.1128/mcb.14.9.6107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Merino A., Buckbinder L., Mermelstein F. H., Reinberg D. Phosphorylation of cellular proteins regulates their binding to the cAMP response element. J Biol Chem. 1989 Dec 15;264(35):21266–21276. [PubMed] [Google Scholar]
  23. Meyer T. E., Habener J. F. Cyclic adenosine 3',5'-monophosphate response element binding protein (CREB) and related transcription-activating deoxyribonucleic acid-binding proteins. Endocr Rev. 1993 Jun;14(3):269–290. doi: 10.1210/edrv-14-3-269. [DOI] [PubMed] [Google Scholar]
  24. Nichols M., Weih F., Schmid W., DeVack C., Kowenz-Leutz E., Luckow B., Boshart M., Schütz G. Phosphorylation of CREB affects its binding to high and low affinity sites: implications for cAMP induced gene transcription. EMBO J. 1992 Sep;11(9):3337–3346. doi: 10.1002/j.1460-2075.1992.tb05412.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Quinn P. G., Wong T. W., Magnuson M. A., Shabb J. B., Granner D. K. Identification of basal and cyclic AMP regulatory elements in the promoter of the phosphoenolpyruvate carboxykinase gene. Mol Cell Biol. 1988 Aug;8(8):3467–3475. doi: 10.1128/mcb.8.8.3467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rayson B. M. [Ca2+]i regulates transcription rate of the Na+/K(+)-ATPase alpha 1 subunit. J Biol Chem. 1991 Nov 15;266(32):21335–21338. [PubMed] [Google Scholar]
  27. Rehfuss R. P., Walton K. M., Loriaux M. M., Goodman R. H. The cAMP-regulated enhancer-binding protein ATF-1 activates transcription in response to cAMP-dependent protein kinase A. J Biol Chem. 1991 Oct 5;266(28):18431–18434. [PubMed] [Google Scholar]
  28. Sheng M., McFadden G., Greenberg M. E. Membrane depolarization and calcium induce c-fos transcription via phosphorylation of transcription factor CREB. Neuron. 1990 Apr;4(4):571–582. doi: 10.1016/0896-6273(90)90115-v. [DOI] [PubMed] [Google Scholar]
  29. Sheng M., Thompson M. A., Greenberg M. E. CREB: a Ca(2+)-regulated transcription factor phosphorylated by calmodulin-dependent kinases. Science. 1991 Jun 7;252(5011):1427–1430. doi: 10.1126/science.1646483. [DOI] [PubMed] [Google Scholar]
  30. Shimomura A., Ogawa Y., Kitani T., Fujisawa H., Hagiwara M. Calmodulin-dependent protein kinase II potentiates transcriptional activation through activating transcription factor 1 but not cAMP response element-binding protein. J Biol Chem. 1996 Jul 26;271(30):17957–17960. doi: 10.1074/jbc.271.30.17957. [DOI] [PubMed] [Google Scholar]
  31. Sun P., Enslen H., Myung P. S., Maurer R. A. Differential activation of CREB by Ca2+/calmodulin-dependent protein kinases type II and type IV involves phosphorylation of a site that negatively regulates activity. Genes Dev. 1994 Nov 1;8(21):2527–2539. doi: 10.1101/gad.8.21.2527. [DOI] [PubMed] [Google Scholar]
  32. Suzuki-Yagawa Y., Kawakami K., Nagano K. Housekeeping Na,K-ATPase alpha 1 subunit gene promoter is composed of multiple cis elements to which common and cell type-specific factors bind. Mol Cell Biol. 1992 Sep;12(9):4046–4055. doi: 10.1128/mcb.12.9.4046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Suzuki T., Fujisawa J. I., Toita M., Yoshida M. The trans-activator tax of human T-cell leukemia virus type 1 (HTLV-1) interacts with cAMP-responsive element (CRE) binding and CRE modulator proteins that bind to the 21-base-pair enhancer of HTLV-1. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):610–614. doi: 10.1073/pnas.90.2.610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wadzinski B. E., Wheat W. H., Jaspers S., Peruski L. F., Jr, Lickteig R. L., Johnson G. L., Klemm D. J. Nuclear protein phosphatase 2A dephosphorylates protein kinase A-phosphorylated CREB and regulates CREB transcriptional stimulation. Mol Cell Biol. 1993 May;13(5):2822–2834. doi: 10.1128/mcb.13.5.2822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Widen S. G., Kedar P., Wilson S. H. Human beta-polymerase gene. Structure of the 5'-flanking region and active promoter. J Biol Chem. 1988 Nov 15;263(32):16992–16998. [PubMed] [Google Scholar]
  36. Yagawa Y., Kawakami K., Nagano K. Cloning and analysis of the 5'-flanking region of rat Na+/K(+)-ATPase alpha 1 subunit gene. Biochim Biophys Acta. 1990 Jul 30;1049(3):286–292. doi: 10.1016/0167-4781(90)90099-n. [DOI] [PubMed] [Google Scholar]
  37. 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]

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

RESOURCES