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| [1.] Iam/Fragment 078 01 - Diskussion Zuletzt bearbeitet: 2014-03-12 19:32:24 Graf Isolan | BauernOpfer, Fragment, Gesichtet, Iam, Luo et al 2005, SMWFragment, Schutzlevel sysop |
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| Untersuchte Arbeit: Seite: 78, Zeilen: 1-15 |
Quelle: Luo et al 2005 Seite(n): 2625, Zeilen: 6-9, l.col:15-27 |
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| [One function of NF-κB is promotion of cell survival through induction of] target genes, whose products inhibit components of the apoptotic machinery in normal and cancerous cells. NF-κB can also prevent programmed necrosis by inducing genes encoding antioxidant proteins. Regardless of mechanism, many cancer cells of either epithelial or hematopoietic origin use NF-κB to achieve resistance to anticancer drugs, radiation, and death cytokines (Luo et al. 2005a).
Two NF-κB activation pathways exist. The first, the classical pathway (Fig. 25), is normally triggered in response to microbial and viral infections or exposure to proinflammatory cytokines that activate the tripartite IKK complex, leading to phosphorylation- induced IκB degradation. This pathway, which mostly targets p50: RelA and p50:c-Rel dimers, depends mainly on IKKβ activity (Li et al. 1999). The second pathway, the alternative pathway, leads to selective activation of p52:RelB dimers by inducing processing of the NF-κB2/p100 precursor protein, which mostly occurs as a heterodimer with RelB in the cytoplasm. This pathway is triggered by certain members of the TNF cytokine family, through selective activation of IKKα homodimers by the upstream kinase NIK (Senftleben et al. 2001). Both pathways regulate cell survival and death (Senftleben and Karin 2002). Li ZW, Chu W, Hu Y, Delhase M, Deerinck T, Ellisman M, Johnson R, Karin M (1999) The IKKbeta subunit of IkappaB kinase (IKK) is essential for nuclear factor kappaB activation and prevention of apoptosis. J Exp Med 189:1839-1845 Luo JL, Kamata H, Karin M (2005a) IKK/NF-kappaB signaling: balancing life and death--a new approach to cancer therapy. J Clin Invest 115:2625-2632 Senftleben U, Cao Y, Xiao G, Greten FR, Krahn G, Bonizzi G, Chen Y, Hu Y, Fong A, Sun SC, Karin M (2001) Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. Science 293:1495-1499 Senftleben U, Karin M (2002) The IKK/NF-kappa B pathway. Crit Care Med 30:S18-S26 |
One function of NF-κB is promotion of cell survival through induction of target genes, whose products inhibit components of the apoptotic machinery in normal and cancerous cells. NF-κB can also prevent programmed necrosis by inducing genes encoding antioxidant proteins. Regardless of mechanism, many cancer cells, of either epithelial or hematopoietic origin, use NF-κB to achieve resistance to anticancer drugs, radiation, and death cytokines. [...]
[...] Two NF-κB activation pathways exist (Figure 1). The first, the classical pathway, is normally triggered in response to microbial and viral infections or exposure to proinflammatory cytokines that activate the tripartite IKK complex, leading to phosphorylation-induced IκB degradation. This pathway, which mostly targets p50:RelA and p50:c-Rel dimers, depends mainly on IKKβ activity (4). The other pathway, the alternative pathway, leads to selective activation of p52:RelB dimers by inducing processing of the NF-κB2/p100 precursor protein, which mostly occurs as a heterodimer with RelB in the cytoplasm. This pathway is triggered by certain members of the TNF cytokine family, through selective activation of IKKα homodimers by the upstream kinase NIK (5). Both pathways regulate cell survival and death (6); [...] 4. Li, Z.W., et al. 1999. The IKKbeta subunit of IkappaB kinase (IKK) is essential for nuclear factor kappaB activation and prevention of apoptosis. J. Exp. Med. 189:1839–1845. 5. Senftleben, U., et al. 2001. Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. Science. 293:1495–1499. 6. Senftleben, U., and Karin, M. 2002. The IKK/NF-kappa B pathway. Crit. Care Med. 30(1 Suppl.):S18–S26. |
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