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. 1993 Sep 11;21(18):4166–4173. doi: 10.1093/nar/21.18.4166

In vitro phosphorylation studies of a conserved region of the transcription factor ATF1.

N Masson 1, J John 1, K A Lee 1
PMCID: PMC310045  PMID: 8414969

Abstract

A large family of mammalian transcription factors including multiple variants of CREB, CREM and ATF1 have been implicated in signal transduction by cAMP and other cellular pathways. Although the roles of some members of the family have been characterised the function of ATF1 is poorly understood. We have identified one or more key serine residues that are required for a phosphorylation-induced conformational change in ATF1. The critical serines map to a putative transcriptional activation domain of ATF1 and affect the stability of ATF1 DNA-binding. Intriguingly phosphorylation is modulated by ATF1 homodimerization and by ATF1 binding to DNA. One of the key serine residues required for ATF1 phosphorylation is not conserved in CREB and CREM suggesting that it is likely to determine some specialised function of ATF1.

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Selected References

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

  1. Bannister A. J., Gottlieb T. M., Kouzarides T., Jackson S. P. c-Jun is phosphorylated by the DNA-dependent protein kinase in vitro; definition of the minimal kinase recognition motif. Nucleic Acids Res. 1993 Mar 11;21(5):1289–1295. doi: 10.1093/nar/21.5.1289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Borrelli E., Montmayeur J. P., Foulkes N. S., Sassone-Corsi P. Signal transduction and gene control: the cAMP pathway. Crit Rev Oncog. 1992;3(4):321–338. [PubMed] [Google Scholar]
  3. Boyle W. J., Smeal T., Defize L. H., Angel P., Woodgett J. R., Karin M., Hunter T. Activation of protein kinase C decreases phosphorylation of c-Jun at sites that negatively regulate its DNA-binding activity. Cell. 1991 Feb 8;64(3):573–584. doi: 10.1016/0092-8674(91)90241-p. [DOI] [PubMed] [Google Scholar]
  4. Brindle P. K., Montminy M. R. The CREB family of transcription activators. Curr Opin Genet Dev. 1992 Apr;2(2):199–204. doi: 10.1016/s0959-437x(05)80274-6. [DOI] [PubMed] [Google Scholar]
  5. Coull J. M., Pappin D. J., Mark J., Aebersold R., Köster H. Functionalized membrane supports for covalent protein microsequence analysis. Anal Biochem. 1991 Apr;194(1):110–120. doi: 10.1016/0003-2697(91)90157-o. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Dwarki V. J., Montminy M., Verma I. M. Both the basic region and the 'leucine zipper' domain of the cyclic AMP response element binding (CREB) protein are essential for transcriptional activation. EMBO J. 1990 Jan;9(1):225–232. doi: 10.1002/j.1460-2075.1990.tb08099.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Foulkes N. S., Borrelli E., Sassone-Corsi P. CREM gene: use of alternative DNA-binding domains generates multiple antagonists of cAMP-induced transcription. Cell. 1991 Feb 22;64(4):739–749. doi: 10.1016/0092-8674(91)90503-q. [DOI] [PubMed] [Google Scholar]
  9. Foulkes N. S., Mellström B., Benusiglio E., Sassone-Corsi P. Developmental switch of CREM function during spermatogenesis: from antagonist to activator. Nature. 1992 Jan 2;355(6355):80–84. doi: 10.1038/355080a0. [DOI] [PubMed] [Google Scholar]
  10. Gonzalez G. A., Menzel P., Leonard J., Fischer W. H., Montminy M. R. Characterization of motifs which are critical for activity of the cyclic AMP-responsive transcription factor CREB. Mol Cell Biol. 1991 Mar;11(3):1306–1312. doi: 10.1128/mcb.11.3.1306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Gorman C. M., Merlino G. T., Willingham M. C., Pastan I., Howard B. H. The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6777–6781. doi: 10.1073/pnas.79.22.6777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Habener J. F. Cyclic AMP response element binding proteins: a cornucopia of transcription factors. Mol Endocrinol. 1990 Aug;4(8):1087–1094. doi: 10.1210/mend-4-8-1087. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Hai T., Curran T. Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3720–3724. doi: 10.1073/pnas.88.9.3720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hunter T., Karin M. The regulation of transcription by phosphorylation. Cell. 1992 Aug 7;70(3):375–387. doi: 10.1016/0092-8674(92)90162-6. [DOI] [PubMed] [Google Scholar]
  17. Hupp T. R., Meek D. W., Midgley C. A., Lane D. P. Regulation of the specific DNA binding function of p53. Cell. 1992 Nov 27;71(5):875–886. doi: 10.1016/0092-8674(92)90562-q. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. Jackson S. P. Regulating transcription factor activity by phosphorylation. Trends Cell Biol. 1992 Apr;2(4):104–108. doi: 10.1016/0962-8924(92)90014-e. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Krek W., Maridor G., Nigg E. A. Casein kinase II is a predominantly nuclear enzyme. J Cell Biol. 1992 Jan;116(1):43–55. doi: 10.1083/jcb.116.1.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lee C. Q., Yun Y. D., Hoeffler J. P., Habener J. F. Cyclic-AMP-responsive transcriptional activation of CREB-327 involves interdependent phosphorylated subdomains. EMBO J. 1990 Dec;9(13):4455–4465. doi: 10.1002/j.1460-2075.1990.tb07896.x. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
  24. Lee K. A., Hai T. Y., SivaRaman L., Thimmappaya B., Hurst H. C., Jones N. C., Green M. R. A cellular protein, activating transcription factor, activates transcription of multiple E1A-inducible adenovirus early promoters. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8355–8359. doi: 10.1073/pnas.84.23.8355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lee K. A. Transcriptional regulation by cAMP. Curr Opin Cell Biol. 1991 Dec;3(6):953–959. doi: 10.1016/0955-0674(91)90113-d. [DOI] [PubMed] [Google Scholar]
  26. Lin A., Frost J., Deng T., Smeal T., al-Alawi N., Kikkawa U., Hunter T., Brenner D., Karin M. Casein kinase II is a negative regulator of c-Jun DNA binding and AP-1 activity. Cell. 1992 Sep 4;70(5):777–789. doi: 10.1016/0092-8674(92)90311-y. [DOI] [PubMed] [Google Scholar]
  27. MacArthur H., Walter G. Monoclonal antibodies specific for the carboxy terminus of simian virus 40 large T antigen. J Virol. 1984 Nov;52(2):483–491. doi: 10.1128/jvi.52.2.483-491.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Manak J. R., de Bisschop N., Kris R. M., Prywes R. Casein kinase II enhances the DNA binding activity of serum response factor. Genes Dev. 1990 Jun;4(6):955–967. doi: 10.1101/gad.4.6.955. [DOI] [PubMed] [Google Scholar]
  29. Masson N., Hurst H. C., Lee K. A. Identification of proteins that interact with CREB during differentiation of F9 embryonal carcinoma cells. Nucleic Acids Res. 1993 Jun 11;21(11):1163–1169. doi: 10.1093/nar/21.5.1163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Meisner H., Czech M. P. Phosphorylation of transcriptional factors and cell-cycle-dependent proteins by casein kinase II. Curr Opin Cell Biol. 1991 Jun;3(3):474–483. doi: 10.1016/0955-0674(91)90076-b. [DOI] [PubMed] [Google Scholar]
  31. Mellon P. L., Clegg C. H., Correll L. A., McKnight G. S. Regulation of transcription by cyclic AMP-dependent protein kinase. Proc Natl Acad Sci U S A. 1989 Jul;86(13):4887–4891. doi: 10.1073/pnas.86.13.4887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Ofir R., Dwarki V. J., Rashid D., Verma I. M. Phosphorylation of the C terminus of Fos protein is required for transcriptional transrepression of the c-fos promoter. Nature. 1990 Nov 1;348(6296):80–82. doi: 10.1038/348080a0. [DOI] [PubMed] [Google Scholar]
  34. Papavassiliou A. G., Chavrier C., Bohmann D. Phosphorylation state and DNA-binding activity of c-Jun depend on the intracellular concentration of binding sites. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11562–11565. doi: 10.1073/pnas.89.23.11562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Pearson R. B., Kemp B. E. Protein kinase phosphorylation site sequences and consensus specificity motifs: tabulations. Methods Enzymol. 1991;200:62–81. doi: 10.1016/0076-6879(91)00127-i. [DOI] [PubMed] [Google Scholar]
  36. Pinna L. A. Casein kinase 2: an 'eminence grise' in cellular regulation? Biochim Biophys Acta. 1990 Sep 24;1054(3):267–284. doi: 10.1016/0167-4889(90)90098-x. [DOI] [PubMed] [Google Scholar]
  37. Pulverer B. J., Kyriakis J. M., Avruch J., Nikolakaki E., Woodgett J. R. Phosphorylation of c-jun mediated by MAP kinases. Nature. 1991 Oct 17;353(6345):670–674. doi: 10.1038/353670a0. [DOI] [PubMed] [Google Scholar]
  38. 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]
  39. Ruppert S., Cole T. J., Boshart M., Schmid E., Schütz G. Multiple mRNA isoforms of the transcription activator protein CREB: generation by alternative splicing and specific expression in primary spermatocytes. EMBO J. 1992 Apr;11(4):1503–1512. doi: 10.1002/j.1460-2075.1992.tb05195.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Sadowski I., Ptashne M. A vector for expressing GAL4(1-147) fusions in mammalian cells. Nucleic Acids Res. 1989 Sep 25;17(18):7539–7539. doi: 10.1093/nar/17.18.7539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. 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]
  42. Tuazon P. T., Traugh J. A. Casein kinase I and II--multipotential serine protein kinases: structure, function, and regulation. Adv Second Messenger Phosphoprotein Res. 1991;23:123–164. [PubMed] [Google Scholar]
  43. Waeber G., Habener J. F. Novel testis germ cell-specific transcript of the CREB gene contains an alternatively spliced exon with multiple in-frame stop codons. Endocrinology. 1992 Oct;131(4):2010–2015. doi: 10.1210/endo.131.4.1396344. [DOI] [PubMed] [Google Scholar]
  44. Waeber G., Meyer T. E., LeSieur M., Hermann H. L., Gérard N., Habener J. F. Developmental stage-specific expression of cyclic adenosine 3',5'-monophosphate response element-binding protein CREB during spermatogenesis involves alternative exon splicing. Mol Endocrinol. 1991 Oct;5(10):1418–1430. doi: 10.1210/mend-5-10-1418. [DOI] [PubMed] [Google Scholar]
  45. Woodgett J. R. Use of synthetic peptides mimicking phosphorylation sites for affinity purification of protein-serine kinases. Methods Enzymol. 1991;200:169–178. doi: 10.1016/0076-6879(91)00137-l. [DOI] [PubMed] [Google Scholar]
  46. Yamamoto K. K., Gonzalez G. A., Menzel P., Rivier J., Montminy M. R. Characterization of a bipartite activator domain in transcription factor CREB. Cell. 1990 Feb 23;60(4):611–617. doi: 10.1016/0092-8674(90)90664-z. [DOI] [PubMed] [Google Scholar]

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