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Science 1 November 1996:
Vol. 274. no. 5288, pp. 782 - 784
DOI: 10.1126/science.274.5288.782
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Reports

An Essential Role for NF-kappa B in Preventing TNF-alpha -Induced Cell Death

Amer A. Beg * and David Baltimore dagger

Studies on mice deficient in nuclear factor kappa B (NF-kappa B) subunits have shown that this transcription factor is important for lymphocyte responses to antigens and cytokine-inducible gene expression. In particular, the RelA (p65) subunit is required for induction of tumor necrosis factor-alpha (TNF-alpha )-dependent genes. Treatment of RelA-deficient (RelA-/-) mouse fibroblasts and macrophages with TNF-alpha resulted in a significant reduction in viability, whereas RelA+/+ cells were unaffected. Cytotoxicity to both cell types was mediated by TNF receptor 1. Reintroduction of RelA into RelA-/- fibroblasts resulted in enhanced survival, demonstrating that the presence of RelA is required for protection from TNF-alpha . These results have implications for the treatment of inflammatory and proliferative diseases.

Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
*   Present address: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.

dagger    To whom correspondence should be addressed.

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Inhibition of Hepatocarcinogenesis by the Deletion of the p50 Subunit of NF-{kappa}B in Mice Administered the Peroxisome Proliferator Wy-14,643.
H. P. Glauert, A. Eyigor, J. C. Tharappel, S. Cooper, E. Y. Lee, and B. T. Spear (2006)
Toxicol. Sci. 90, 331-336
   Abstract »    Full Text »    PDF »
Reduction of experimental necrotizing enterocolitis with anti-TNF-{alpha}.
M. D. Halpern, J. A. Clark, T. A. Saunders, S. M. Doelle, D. M. Hosseini, A. M. Stagner, and B. Dvorak (2006)
Am J Physiol Gastrointest Liver Physiol 290, G757-G764
   Abstract »    Full Text »    PDF »
TNF-{alpha} in Cancer Treatment: Molecular Insights, Antitumor Effects, and Clinical Utility..
R. van Horssen, T. L. M. ten Hagen, and A. M. M. Eggermont (2006)
Oncologist 11, 397-408
   Abstract »    Full Text »    PDF »
Antianoikis Effect of Nuclear Factor-{kappa}B through Up-regulated Expression of Osteoprotegerin, BCL-2, and IAP-1.
M. Toruner, M. Fernandez-Zapico, J. J. Sha, L. Pham, R. Urrutia, and L. J. Egan (2006)
J. Biol. Chem. 281, 8686-8696
   Abstract »    Full Text »    PDF »
Glucocorticoids enhance cytotoxicity of cisplatin via suppression of NF-{kappa}B activation in the glucocorticoid receptor-rich human cervical carcinoma cell line SiHa.
Y.-S. Lu, P.-Y. Yeh, S.-E. Chuang, M. Gao, M.-L. Kuo, and A.-L. Cheng (2006)
J. Endocrinol. 188, 311-319
   Abstract »    Full Text »    PDF »
A Splice Variant of Stress Response Gene ATF3 Counteracts NF-{kappa}B-dependent Anti-apoptosis through Inhibiting Recruitment of CREB-binding Protein/p300 Coactivator.
B. Hua, M. Tamamori-Adachi, Y. Luo, K. Tamura, M. Morioka, M. Fukuda, Y. Tanaka, and S. Kitajima (2006)
J. Biol. Chem. 281, 1620-1629
   Abstract »    Full Text »    PDF »
Cisplatin Mimics ARF Tumor Suppressor Regulation of RelA (p65) Nuclear Factor-{kappa}B Transactivation.
K. J. Campbell, J. M. Witty, S. Rocha, and N. D. Perkins (2006)
Cancer Res. 66, 929-935
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PAK4 Functions in Tumor Necrosis Factor (TNF) {alpha}-induced Survival Pathways by Facilitating TRADD Binding to the TNF Receptor.
X. Li and A. Minden (2005)
J. Biol. Chem. 280, 41192-41200
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Enhancement of Sensitivity to Tumor Necrosis Factor {alpha} in Non-Small Cell Lung Cancer Cells with Acquired Resistance to Gefitinib.
K. Ando, T. Ohmori, F. Inoue, T. Kadofuku, T. Hosaka, H. Ishida, T. Shirai, K. Okuda, T. Hirose, N. Horichi, et al. (2005)
Clin. Cancer Res. 11, 8872-8879
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Nuclear Factor-{kappa}B-Mediated Cell Survival Involves Transcriptional Silencing of the Mitochondrial Death Gene BNIP3 in Ventricular Myocytes.
D. Baetz, K. M. Regula, K. Ens, J. Shaw, S. Kothari, N. Yurkova, and L. A. Kirshenbaum (2005)
Circulation 112, 3777-3785
   Abstract »    Full Text »    PDF »
NF-{kappa}B and FLIP in arsenic trioxide (ATO)-induced apoptosis in myelodysplastic syndromes (MDSs).
D. M. B. Kerbauy, V. Lesnikov, N. Abbasi, S. Seal, B. Scott, and H. J. Deeg (2005)
Blood 106, 3917-3925
   Abstract »    Full Text »    PDF »
TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo.
J.-H. Shim, C. Xiao, A. E. Paschal, S. T. Bailey, P. Rao, M. S. Hayden, K.-Y. Lee, C. Bussey, M. Steckel, N. Tanaka, et al. (2005)
Genes & Dev. 19, 2668-2681
   Abstract »    Full Text »    PDF »
Distinct Role of Calmodulin and Calmodulin-dependent Protein Kinase-II in Lipopolysaccharide and Tumor Necrosis Factor-{alpha}-mediated Suppression of Apoptosis and Antiapoptotic c-IAP2 Gene Expression in Human Monocytic Cells.
S. Mishra, J. P. Mishra, K. Gee, D. C. McManus, E. C. LaCasse, and A. Kumar (2005)
J. Biol. Chem. 280, 37536-37546
   Abstract »    Full Text »    PDF »
Protein turnover in cardiac cell growth and survival.
N. Hedhli, M. Pelat, and C. Depre (2005)
Cardiovasc Res 68, 186-196
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Differential effects of proteasome inhibition by bortezomib on murine acute graft-versus-host disease (GVHD): delayed administration of bortezomib results in increased GVHD-dependent gastrointestinal toxicity.
K. Sun, D. E. C. Wilkins, M. R. Anver, T. J. Sayers, A. Panoskaltsis-Mortari, B. R. Blazar, L. A. Welniak, and W. J. Murphy (2005)
Blood 106, 3293-3299
   Abstract »    Full Text »    PDF »
Epidermal growth factor activates nuclear factor-{kappa}B in human proximal tubule cells.
U. Haussler, G. von Wichert, R. M. Schmid, F. Keller, and G. Schneider (2005)
Am J Physiol Renal Physiol 289, F808-F815
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Expression of an Uncleavable N-terminal RasGAP Fragment in Insulin-secreting Cells Increases Their Resistance toward Apoptotic Stimuli without Affecting Their Glucose-induced Insulin Secretion.
J.-Y. Yang, J. Walicki, A. Abderrahmani, M. Cornu, G. Waeber, B. Thorens, and C. Widmann (2005)
J. Biol. Chem. 280, 32835-32842
   Abstract »    Full Text »    PDF »
A c-Rel subdomain responsible for enhanced DNA-binding affinity and selective gene activation.
S. Sanjabi, K. J. Williams, S. Saccani, L. Zhou, A. Hoffmann, G. Ghosh, S. Gerondakis, G. Natoli, and S. T. Smale (2005)
Genes & Dev. 19, 2138-2151
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Interferon Induces NF-{kappa}B-inducing Kinase/Tumor Necrosis Factor Receptor-associated Factor-dependent NF-{kappa}B Activation to Promote Cell Survival.
C. H. Yang, A. Murti, and L. M. Pfeffer (2005)
J. Biol. Chem. 280, 31530-31536
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Tumor Necrosis Factor Receptor 2 (TNFR2) Signaling Is Negatively Regulated by a Novel, Carboxyl-terminal TNFR-associated Factor 2 (TRAF2)-binding Site.
A. P. Grech, S. Gardam, T. Chan, R. Quinn, R. Gonzales, A. Basten, and R. Brink (2005)
J. Biol. Chem. 280, 31572-31581
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LNFPIII/LeX-Stimulated Macrophages Activate Natural Killer Cells via CD40-CD40L Interaction.
O. Atochina and D. Harn (2005)
Clin. Vaccine Immunol. 12, 1041-1049
   Abstract »    Full Text »    PDF »


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