An Oxidant Sensor at the Plasma Membrane

  • Axel Knebel
  • Mihail Iordanov
  • Hans J. Rahmsdorf
  • Peter Herrlich
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 387)


The expression of genes is predominantly determined by conditions of the microenvironment of cells. Prime examples of such regulation are found in embryonic development of all multicellular organisms and also in the adult when various cytokines and hormones exert highly inducer-specific influences on genes. The naturally occurring regulating agents interact with specific receptors: e.g., the retinoids, vitamin D3, thyroid hormones and the steroid hormones with appropriate nuclear receptors (RARs, RXRs, VDR and the specific steroid hormone receptors), or the members of the large TGFβ and FGF families with their respective cell surface receptors. While nuclear receptors act as transcription factors themselves and select their genes by receptor-specific recognition elements, the growth factors induce, through their cell surface receptors, a complex process of signal transduction to the nucleus (for reviews see Beato, 1989; Karin, 1994; Gilbert, 1994; Angel and Herrlich, 1994; McCormick, 1995; Howe and Weiss, 1995; Ullrich and Simon, 1995).


Heat Shock Factor Potassium Permanganate Reactive Oxygen Intermediate Familial Amyotrophic Lateral Sclerosis Transcription Factor NFKB 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abate, C, Patel, L., Rauscher III, F. J., and Curran, T. (1990). Redox regulation of Fos and Jun DNA-binding activity in vitro. Science 249, 1157–1161.PubMedCrossRefGoogle Scholar
  2. Ames, B. N. (1989). Endogenous oxidative DNA damage, aging and cancer. Free Radic. Res. Commun. 7, 121–128.PubMedCrossRefGoogle Scholar
  3. Angel, P., and Herrlich, P. (1994). The Fos and Jun families of transcription factors. In: “CRC-press”, Boca-Raton, FL, U.S.A.Google Scholar
  4. Beato, M. (1989). Gene regulation by steroid hormones. Cell 56, 335–344.PubMedCrossRefGoogle Scholar
  5. Cadenas, E. (1989). Biochemistry of oxygen toxicity. Annu. Rev. Biochem. 58, 79–110.PubMedCrossRefGoogle Scholar
  6. Cerutti, P. A. (1985). Prooxidant states and tumor promotion. Science 227, 375–381.PubMedCrossRefGoogle Scholar
  7. Chen. W. S., Lazar, C. S., Poenie, M., Tsien, R. Y., Gill, G. N., and Rosenfeld, M. G. (1987). Requirement for intrinsic protein tyrosine kinase in the immediate and late actions of the EGF receptor. Nature 328, 820–823.PubMedCrossRefGoogle Scholar
  8. Deng, H.-X., Hentati, A., Tainer, J. A., Iqbal, Z., Cayabyab, A., Hung, W.-Y, Getzoff, E. D., Hu, P., Herzfeldt, B., Roos, R. P., Warner, C, Deng, G., Soriano, E., Smyth, C., Parge, H. E., Ahmed, A., Roses, A. D., Hallewell, R. A., Pericak-Vance, M. A., and Siddique, T. (1993). Amyotrophic lateral sclerosis and structural defects in Cu, Zn Superoxide dismutase. Science 261, 1047–1051.PubMedCrossRefGoogle Scholar
  9. Devary, Y, Gottlieb, R. A., Smeal, T., and Karin, M. (1992). The mammalian ultraviolet response is triggered by activation of Src tyrosine kinases. Cell 71, 1081–1091.PubMedCrossRefGoogle Scholar
  10. Gilbert, S. F. (1994). Developmental Biology. (Sunderland, MA, U.S.A.: Sinauer Associates), pp. 531–622.Google Scholar
  11. Greenlund, L. J. S., Deckwerth, T. L., and Johnson Jr., E. M. (1995). Superoxide dismutase delays neuronal apoptosis: A role for reactive oxygen species in programmed neuronal death. Neuron 14, 303–315.PubMedCrossRefGoogle Scholar
  12. Heffetz, D., Rutter, W. J., and Zick, Y (1992). The insulinomimetic agents H2O2 and vanadate stimulate tyrosine phosphorylation of potential target proteins for the insulin receptor kinase in intact cells. Biochem. J. 288, 631–635.PubMedGoogle Scholar
  13. Heuchel, R., Radtke, F., Georgiev, O., Stark, G., Aguet, M., and Schaffner, W. (1994). The transcription factor MTF-1 is essential for basal and heavy metal-induced metallothionein gene expression. EMBO J. 13, 2870–2875.PubMedGoogle Scholar
  14. Howe, L. R., and Weiss, A. (1995). Multiple kinases mediate T-cell-receptor signaling. TIBS 20, 59–64.PubMedGoogle Scholar
  15. Joenje, H. (1989). Genetic toxicology of oxygen. Mutation Res. 219, 193–208.PubMedCrossRefGoogle Scholar
  16. Kaina, B., Lohrer, H., Karin, M., and Herrlich, P. (1990). Overexpressed human metallothionein IIA gene protects Chinese hamster ovary cells from killing by alkylating agents. Proc. Natl. Acad. Sci. U.S.A. 87, 2710–2714.PubMedCrossRefGoogle Scholar
  17. Karin, M. (1994). Signal transduction from the cell surface to the nucleus through the phosphorylation of transcription factors. Curr. Opinion in Cell Biol. 6, 415–424.CrossRefGoogle Scholar
  18. Kelley, S. L., Basu, A., Teicher, B. A., Hacker, M. P., Hamer, D. H., and Lazo, J. S. (1988). Overexpression of metallothionein confers resistance to anticancer drugs. Science 241, 1813–1815.PubMedCrossRefGoogle Scholar
  19. Lis, J., and Wu, C. (1993). Protein traffic on the heat shock promoter: Parking, stalling, and trucking along. Cell 74, 1–4.PubMedCrossRefGoogle Scholar
  20. McCormick, F. (1995). Ras signaling and NF1. Curr. Opinion in Gen. and Dev. 5, 51–55.CrossRefGoogle Scholar
  21. Meister, A., and Anderson, M. E. (1983). Glutathione. Ann. Rev. Biochem. 52, 711–760.PubMedCrossRefGoogle Scholar
  22. Meyer, M., Schreck, R., and Baeuerle, P. A. (1993). H2O2 and antioxidants have opposite effects on activation of NF-KB and AP-1 in intact cells: AP-1 as secondary antioxidant-responsive factor. EMBO J. 12, 2005–2015.PubMedGoogle Scholar
  23. Molitor, J. A., Ballard, D. W., and Greene, W. C. (1991). ΚB-specific DNA binding proteins are differentially inhibited by enhancer mutations and biological oxidation. The New Biol. 3, 987–996.Google Scholar
  24. Oehler, T., Pintzas, A., Stumm, S., Darling, A., Gillespie, D., and Angel, P. (1993). Mutation of a phosphorylation site in the DNA-binding domain is required for redox-independent transactivation of API-dependent genes by v-Jun. Oncogene 8, 1141–1147.PubMedGoogle Scholar
  25. Okey, A. B., Riddick, D. S., and Harper, P. A. (1994). Molecular biology of the aromatic hydrocarbon (dioxin) receptor. TiPS 15, 226–232.PubMedGoogle Scholar
  26. Radler-Pohl, A., Sachsenmaier, C, Gebel, S., Auer, H.-R, Bruder, J. T., Rapp, U., Angel, P., Rahmsdorf, H. J., and Herrlich, P. (1993). UV-induced activation of AP-1 involves obligatory extranuclear steps including Raf-1 kinase. EMBO J. 12, 1005–1012.PubMedGoogle Scholar
  27. Rosen, D. R., Siddique, T., Patterson, D., Figlewicz, D. A., Sapp, P., Hentati, A., Donaldson, D., Goto, J., O’Regan, J. P., Deng, H.-X., Rahmani, Z., Krizus, A., McKenna-Yasek, D., Cayabyab, A., Gaston, S. M., Berger, R., Tanzi, R. E., Halperin, J. J., Herzfeldt, B., Van den Bergh, R., Hung, W.-Y., Bird, T., Deng, G., Mulder, D. W., Smyth, C, Laing, N. G., Soriano, E., Pericak-Vance, M. A., Haines, J., Rouleau, G. A., Gusella, J. S., Horvitz, H. R., and Brown Jr, R. H. (1993). Mutations in Cu/Zn Superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362, 59–62.PubMedCrossRefGoogle Scholar
  28. Sachsenmaier, C, Radler-Pohl, A., Zinck, R., Nordheim, A., Herrlich, P., and Rahmsdorf, H. J. (1994). Involvement of growth factor receptors in the mammalian UVC response. Cell 78, 963–972.PubMedCrossRefGoogle Scholar
  29. Schenk, H., Klein, M., Erdbrügger, W., Dröge, W., and Schulze-Osthoff, K. (1994). Distinct effects of thioredoxin and antioxidants on the activation of transcription factor NF-kB and AP-1. Proc. Natl. Acad. Sci. U.S.A. 91, 1672–1676.PubMedCrossRefGoogle Scholar
  30. Schieven, G. L., Mittler, R. S., Nadler, S. G., Kirihara, J.M., Bolen, J. B., Kanner, S. B., and Ledbetter, J. A. (1994). ZAP-70 tyrosine kinase, CD45, and T cell receptor involvement in UV-and H2O2-induced T cell signal transduction. J. Biol. Chem. 269, 20718–20726.PubMedGoogle Scholar
  31. Schmidt, K. N., Amstad, P., Cerutti, P. and Baeuerle, P.A. (1995). The roles of hydrogen peroxide and Superoxide as messengers in the activation of transcription factor NF-κB. Chemistry & Biology 2, 13–22.CrossRefGoogle Scholar
  32. Sistonen, L., Sarge, K. D., and Morimoto, R. I. (1994). Human heat shock factors 1 and 2 are differentially activated and can synergistically induce hsp70 gene transcription. Mol. Cell. Biol. 14, 2087–2099.PubMedGoogle Scholar
  33. Staal, F. J. T., Roederer, M., Herzenberg, L. A., and Herzenberg, L. A. (1990). Intracellular thiols regulate activation of nuclear factor KB and transcription of human immunodeficiency virus. Proc. Natl. Acad. Sci. U.S.A. 87, 9943–9947.PubMedCrossRefGoogle Scholar
  34. Sullivan, S. G., Chiu, D. T., Errasfa, M., Wang, J. M., Qi, J. S., and Stern, A. (1994). Effects of H2O2 on protein tyrosine phosphatase activity in HER14 cells. Free Radie. Biol. Med. 16, 399–403.CrossRefGoogle Scholar
  35. Swanson, H. L, and Bradfield, C. A. (1993). The AH-receptor: Genetics, structure and function. Pharmacogenetics 3, 213–230.PubMedCrossRefGoogle Scholar
  36. Toledano, M. B., and Leonhard, W. J. (1991). Modulation of transcription factor NF-KB binding activity by oxidation-reduction in vitro. Proc. Natl. Acad. Sci. U.S.A. 88, 4328–4332.PubMedCrossRefGoogle Scholar
  37. Ullrich, A. and Simon (1995). Cell regulation. Curr. Opinion in Cell Biol. 7, 145–196.CrossRefGoogle Scholar
  38. Wasilenko, W. J., Non, M., Testerman, N., and Weber, M. J. (1990). Inhibition of epidermal growth factor receptor biosynthesis caused by the sre oncogene product, pp60v-sre. Mol. Cell. Biol. 10, 1254–1258.PubMedGoogle Scholar
  39. Xanthoudakis, S., Miao, G., Wang, F., Pan., Y.-C. E., and Curran, T. (1992). Redox-activation of Fos-Jun DNA binding activity is mediated by a DNA repair enzyme. EMBO J. 11, 3323–3335.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Axel Knebel
    • 1
  • Mihail Iordanov
    • 1
  • Hans J. Rahmsdorf
    • 1
  • Peter Herrlich
    • 1
  1. 1.Forschungszentrum KarlsruheInstitut für GenetikKarlsruheGermany

Personalised recommendations