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The Transcription Factor TCF/Elk-1

A Nuclear Sensor of Changes in the Cellular Redox Status
  • Judith M. Müller
  • Michael A. Cahill
  • Alfred Nordheim
  • Patrick A. Baeuerle
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 387)

Abstract

The ternary complex factor (TCF) and the serum response factor (SRF) are nuclear transcription factors which are essential for efficient signal transduction via the serum response element SRE in the c-fos promoter. Their activation leads to a rapid induction of c-fos gene expression. Activation of mitogen-activated protein kinases (MAPK) by signalling cascades and subsequent TCF phosphorylation are known to be essential steps in this transcriptional activation.

In transient transfections we could show activation of a SRE dependent promoter following treatment of HeLa cells with either the oxidant H2O2 or various antioxidants. This activation is dependent on the presence of both an intact SRE as well as a TCF binding site. In gel shifts we observed changes in the migration of ternary complexes which were due to hyperphosphorylation of TCF/Elk-1. In-gel kinase assays showed an activation of MAPK Ser/Thr kinase activity by both oxidant and antioxidant stimuli, which temporally correlates with the appearance of hyperphosphorylated TCF/Elk-1. Thus antagonistic intracellular redox changes can lead to the same functional modulation of the nuclear transcription factor TCF/Elk-1 that was previously described following mitogenic stimuli.

Keywords

HeLa Cell Myelin Basic Protein Serum Response Factor Nuclear Transcription Factor Pyrrolidine Dithiocarbamate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abreviations

BHA

butylated hydroxyanisole

FCS

fetal calf serum

kDa

kilo dalton

MAPkinase

mitogen activated proteine kinase

MBP

myelin basic protein

NAC

N-acetyl L-cysteine

PPase

phosphatase

PDTC

pyrrolidine dithiocarbamate

ROI

reactive oxygen intermediates

SRE

serum response element

SRF

serum responsive factor

TCF

ternary complex factor

wt

wildtype

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References

  1. 1.
    Abate, C. Patel, L. Rauscher, F. J. III, & Curran, T. Science 249, 1157–1161 (1990).PubMedCrossRefGoogle Scholar
  2. 2.
    Amstad, P. A. Krupitza, G. & Cerutti, P. A. Cancer Res. 52, 3952–3960 (1992).PubMedGoogle Scholar
  3. 3.
    Baccarini, M. Sabatini, D. M. App, H. & Stanley, E. R. EMBOJ. 9, 3649–3657 (1990).Google Scholar
  4. 4.
    Bergelson, S. Pinkus, R. & Daniel, V. Oncogene 9, 565–571 (1994).PubMedGoogle Scholar
  5. 5.
    Cerutti, P.A. Science 227, 375–381 (1985).PubMedCrossRefGoogle Scholar
  6. 6.
    Chao, T.-S. O. Byron, K. L. Lee, K.-M. Villereal, M. & Rosner, M. R.J. Biol. Chem. 261, 19876–19883 (1992).Google Scholar
  7. 7.
    Chen, R.-H. Sarnecki, C. & Blenis, J. Mol. Cell. Biol. 12, 915–927 (1992).PubMedGoogle Scholar
  8. 8.
    Dröge, W. et al., FASEBJ. 8, 1131–1138 (1994).Google Scholar
  9. 9.
    Gamou, S. and Shimizu, N. FEBS Letters 357, 161–164 (1995).PubMedCrossRefGoogle Scholar
  10. 10.
    Gille, H. G. Sharrocks, A. D. & Shaw, P. E. Nature 358, 414–417 (1992).PubMedCrossRefGoogle Scholar
  11. 11.
    Graham, R. & Gilman, M. Science 151, 189–192 (1991).CrossRefGoogle Scholar
  12. 12.
    Halliwell, B., & Gutteridge, J.M.C. Free Radicals in Biology and Medicine (Clarendon Press, Oxford, 1989).Google Scholar
  13. 13.
    Herrera, R.E., Shaw, P.E., & Nordheim, A. Nature 340, 68–70 (1989).PubMedCrossRefGoogle Scholar
  14. 14.
    Hill, C. S. Marais, R. John, S. Wynne, J. Dalton, S. & Treisman, R. Cell 73, 395–406 (1993).PubMedCrossRefGoogle Scholar
  15. 15.
    Hug, H. and Sarre, T.F. Biochem. J. 291, 329–343 (1993).PubMedGoogle Scholar
  16. 16.
    Janknecht, R. Ernst, W. H. Pingoud, V. & Nordheim, A. EMBOJ. 12, 5097–5104 (1993).Google Scholar
  17. 17.
    Karin, M. Curr. Opin. Cell Biol. 6, 415–424 (1994).PubMedCrossRefGoogle Scholar
  18. 18.
    Kuge, S. & Jones, N. EMBOJ. 13, 655–664 (1994).Google Scholar
  19. 19.
    Kyriakis, J. M. et al., Nature 369, 156–160 (1994).PubMedCrossRefGoogle Scholar
  20. 20.
    Li, Y. & Jaiswal, A. K. Biochem. Biophys. Res. Comm. 188, 992–996 (1992).PubMedCrossRefGoogle Scholar
  21. 21.
    Macleod, K. Leprince D. & Strehlin, D. Trends Biochem. Sci. 17, 251–256 (1992).PubMedCrossRefGoogle Scholar
  22. 22.
    Marais, R. Wynne, J. & Treisman, R. Cell 73, 381–393 (1993).PubMedCrossRefGoogle Scholar
  23. 23.
    Meyer, M. Schreck, R. & Baeuerle, P. A. EMBOJ. 12, 2005–2015 (1993).Google Scholar
  24. 24.
    Müller, J. M. Cahill, M. A. Baeuerle, P. A. & Nordheim, A. submitted.Google Scholar
  25. 25.
    Nose, K. et al. Eur. J. Biochem. 201, 99–106 (1991).PubMedCrossRefGoogle Scholar
  26. 26.
    Pahl, H. L. & Baeuerle, P. A. Bioessays 16, 497–502 (1994).PubMedCrossRefGoogle Scholar
  27. 27.
    Papavassiliou, A. G. & Bohmann, D. Meth. Mol & Cell. Bio. 3, 149–152 (1990).Google Scholar
  28. 28.
    Perez-Albuerne, E. D. Schatteman, G. Sanders, L. K. & Nathans, D. Proc. Natl. Acad. Sci. USA 90, 11960–11964 (1993).PubMedCrossRefGoogle Scholar
  29. 29.
    Rao, G. N. Lasségue, B. Griendling, K. K. Wayne, R. & Berk, B. C. Nucl Acids Res. 21, 1259–1263 (1993).PubMedCrossRefGoogle Scholar
  30. 30.
    Sachsenmaier, C. et al., Cell 78, 963–972 (1994).PubMedCrossRefGoogle Scholar
  31. 31.
    Schmidt, K. N., Amstad, P., Cerutti, P. A. & Baeuerle, P. A. Chem.& Biol. 2, 13–22 (1995).CrossRefGoogle Scholar
  32. 32.
    Schreck, R. Meier, B. Männel, D. N. Dröge, W. & Baeuerle, P, A. J. Exp. Med. 175, 1181–1194 (1992).PubMedCrossRefGoogle Scholar
  33. 33.
    Schreck, R. Rieber, P. & Baeuerle, P. A. EMBOJ. 10, 2247–2258 (1991).Google Scholar
  34. 34.
    Shaw, P. E. Schröter, H. & Nordheim, A. Cell 56, 563–572 (1989).PubMedCrossRefGoogle Scholar
  35. 35.
    Shibanuma, M. Kuroki, T. & Nose, K. Oncogene 3, 17–21 (1988).Google Scholar
  36. 36.
    Sies, H. Eur. J. Biochem. 215, 213–219 (1993).PubMedCrossRefGoogle Scholar
  37. 37.
    Stein, B. Rahmsdorf, H. J. Steffen, A. Litfin, M. & Herrlich, P. Mol. Cell. Biol. 9, 5169–5181 (1989).PubMedGoogle Scholar
  38. 38.
    Stevenson, M. A. Pollock, S. S. Coleman, C. N. & Calderwood, S. K. Cancer Res. 54, 12–15 (1994).PubMedGoogle Scholar
  39. 39.
    Treisman, R. Cell 46, 567–574 (1986).PubMedCrossRefGoogle Scholar
  40. 40.
    Treisman, R. Curr. Opin. Genet. & Dev. 4, 96–101 (1994).CrossRefGoogle Scholar
  41. 41.
    Treisman, R. Trends Biochem. Sci. 17, 423–426 (1992).PubMedCrossRefGoogle Scholar
  42. 42.
    Zinck, R. Hipskind, R. A. Pingoud, V. & Nordheim, A. EMBOJ. 12, 2377–2387 (1993).Google Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Judith M. Müller
    • 1
  • Michael A. Cahill
    • 2
  • Alfred Nordheim
    • 2
  • Patrick A. Baeuerle
    • 1
  1. 1.Institute of BiochemistryAlbert-Ludwig-UniversityFreiburgGermany
  2. 2.Institute for Molecular BiologyHannover Medical SchoolHannoverGermany

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