Identification of Hydrogen Peroxide as the Relevant Messenger in the Activation Pathway of Transcription Factor NF-κB

  • Kerstin N. Schmidt
  • Paul Amstad
  • Peter Cerutti
  • Patrick A. Baeuerle
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 387)


The inducible higher eukaryotic transcription factor NF-κB is activated by a large variety of distinct simuli [1–3]. In unstimulated cells, this factor resides in a latent form in the cytoplasm [4]. Latency is achieved by association of the DNA-binding NF-κB dimer with an inhibitory subunit, called IκB [5]. IΚB suppresses DNA-binding and nuclear transport of NF-κB. Upon stimulation of cells, IκB is phosphorylated and proteolytically degraded [6–9]. Both reactions are required for activation [10]. The released NF-κB is then translocated to the nucleus where it initiates transcription of target genes. Among the numerous proteins which are induced by a concerted action of NF-kB with other transcription factors are cytokines, chemokines, cell adhesion molecules, hematopoetic growth factors and receptors, histocompatibility antigens and acute phase proteins [1–3]. While NF-κB may be indispensable as inducer of many immediate-early inflammatory and immune reactions, the transcription factor is likely to play a fatal role in certain diseases and syndromes that involve an abberrant expression of inflammatory cytokines [22–24].


Tumor Necrosis Factor Electrophoretic Mobility Shift Assay Okadaic Acid Total Cell Extract Inhibitory Subunit 
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  1. 1.
    Baeuerle, P. A. (1991). Biochem. Biophys. Acta 1072, 63–8.PubMedGoogle Scholar
  2. 2.
    Grilli, M., Jason, J.-S. & Lenardo, M.J. (1993). Int. Rev. Cytol 143, 1–62.PubMedCrossRefGoogle Scholar
  3. 3.
    Baeuerle, P. A. & Henkel, T. (1994). Annu. Rev. Immunol. 12, 141–179.PubMedCrossRefGoogle Scholar
  4. 4.
    Baeuerle, P. A. & Baltimore, D. (1988a). Cell 53, 211–217.PubMedCrossRefGoogle Scholar
  5. 5.
    Baeuerle, P. A. & Baltimore, D. (1988b). Science 242, 540–546.PubMedCrossRefGoogle Scholar
  6. 6.
    Sun, S. C, Ganchi, P. A., Ballard, D. W., & Greene, W. C. (1993). Science 259, 1912–1915.PubMedCrossRefGoogle Scholar
  7. 7.
    Brown, K., Park, S., Kanno, T., Franzoso, T. & Siebenlist, U. (1993). Proc. Natl. Acad. Sci. U.S.A. 90, 2532–2536.PubMedCrossRefGoogle Scholar
  8. 8.
    Beg, A. A., Ruben, S. M. Scheinman, R. I., Haskill, S., Rosen, C. A. & Baldwin, A. J. (1992). Genes Dev. 6, 1899–1913.PubMedCrossRefGoogle Scholar
  9. 9.
    Henkel, T., Machleidt, T., Alkalay, I. Krönke, M. Ben-Neriah, Y. & Baeuerle, P. A. (1993). Nature 365, 182–185.PubMedCrossRefGoogle Scholar
  10. 10.
    Traenckner, E. B.-M., Wilk, S. & Baeuerle, P. A. (1994). EMBOJ. 13, 101–109.Google Scholar
  11. 11.
    Schreck, R. & Baeuerle, P. A. (1991). Trends in Cell Biol. 1, 39–42.CrossRefGoogle Scholar
  12. 12.
    Schreck, R., Albermann, K. & Baeuerle, P.A. (1992). Free Rad. Res. Comms. 17, 221–237.CrossRefGoogle Scholar
  13. 13.
    Meyer, M., Schreck, R., Müller, J. M. & Baeuerle, P. A. (1993). Oxidative Stress on Cell Activation and Viral Infection. (C. Pasquier et al., ed), pp. 217–235, Birkhäuser Verlag AG, Basel.Google Scholar
  14. 14.
    Schreck, R., Meier, B., Männel, D., Dröge, W. & Baeuerle, P.A. (1992). J. Exp. Med. 175, 1181–1194.PubMedCrossRefGoogle Scholar
  15. 15.
    Meyer, M., Schreck, R. & Baeuerle, P.A. (1993). EMBOJ. 12, 2005–2015.Google Scholar
  16. 16.
    Schreck, R., Rieber, P. & Baeuerle, P.A. (1991). EMBOJ. 10, 2247–2258.Google Scholar
  17. 17.
    Staal, F. J. T., Roederer, M. & Herzenberg, L. A. (1991). Proc. Natl. Acad. Sci. USA 87, 9943–9947.CrossRefGoogle Scholar
  18. 18.
    Mihm, S., Ennen, J., Pessara, U., Kurth, R. & Droege, W. (1991). AIDS 5, 497–503.PubMedCrossRefGoogle Scholar
  19. 19.
    Menon, S.D., Qin, S., Guy, G.R. & Tan, Y.H. (1993). J. Biol. Chem. 268, 26805–26812.PubMedGoogle Scholar
  20. 20.
    Amstad, P., Peskin, A. Shah, G., Mirault, M.-E., Moret, R., Zbinden, I. & Cerutti, P. (1991). Biochem. J. 30, 9305–9113.CrossRefGoogle Scholar
  21. 21.
    Amstad, P., Moret, R. & Cerutti, P. (1993). J. Biol. Chem. 269, 1–4.Google Scholar
  22. 22.
    Sendtner, M. & Thoenen, H. (1994). Curr. Biol. 4, 1036–1039.PubMedCrossRefGoogle Scholar
  23. 23.
    Avraham, K. B., Schickler, M., Sapoznikov, D. Yarom, R. & Groner, Y. (1988). Cell 53, 211–217.CrossRefGoogle Scholar
  24. 24.
    Rosen, D.R. et al. (1993). Nature 362. 59–62.PubMedCrossRefGoogle Scholar
  25. 25.
    Halliwell, B. & Gutteridge, J.M.C. (1989). Free Radical in Biology and Medicine. (2nd edn) Clarendon Press, Oxford.Google Scholar
  26. 26.
    Schreiber, E., Matthias, P., Müller, M.M. & Schaffner, W. (1989). Nucl Acids Res. 17, 6419.PubMedCrossRefGoogle Scholar
  27. 27.
    Zabel, U., Schreck, R. & Baeuerle, P.A. (1991). J. Biol. Chem. 266, 252–260.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Kerstin N. Schmidt
    • 1
  • Paul Amstad
    • 2
  • Peter Cerutti
    • 2
  • Patrick A. Baeuerle
    • 1
  1. 1.Institute of BiochemistryUniversity of FreiburgFreiburgGermany
  2. 2.Department of CarcinogenesisSwiss Institute for Experimental Cancer ResearchÉpalinges s. LausanneSwitzerland

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