Identification of Hydrogen Peroxide as the Relevant Messenger in the Activation Pathway of Transcription Factor NF-κB
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 . Latency is achieved by association of the DNA-binding NF-κB dimer with an inhibitory subunit, called IκB . 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 . 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].
KeywordsTumor Necrosis Factor Electrophoretic Mobility Shift Assay Okadaic Acid Total Cell Extract Inhibitory Subunit
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- 10.Traenckner, E. B.-M., Wilk, S. & Baeuerle, P. A. (1994). EMBOJ. 13, 101–109.Google Scholar
- 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
- 15.Meyer, M., Schreck, R. & Baeuerle, P.A. (1993). EMBOJ. 12, 2005–2015.Google Scholar
- 16.Schreck, R., Rieber, P. & Baeuerle, P.A. (1991). EMBOJ. 10, 2247–2258.Google Scholar
- 21.Amstad, P., Moret, R. & Cerutti, P. (1993). J. Biol. Chem. 269, 1–4.Google Scholar
- 25.Halliwell, B. & Gutteridge, J.M.C. (1989). Free Radical in Biology and Medicine. (2nd edn) Clarendon Press, Oxford.Google Scholar