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Science 11 September 1998:
Vol. 281. no. 5383, pp. 1680 - 1683
DOI: 10.1126/science.281.5383.1680
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Reports

NF-kappa B Antiapoptosis: Induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to Suppress Caspase-8 Activation

Cun-Yu Wang, * Marty W. Mayo, Robert G. Korneluk, David V. Goeddel, Albert S. Baldwin Jr. *

Tumor necrosis factor alpha  (TNF-alpha ) binding to the TNF receptor (TNFR) potentially initiates apoptosis and activates the transcription factor nuclear factor kappa B (NF-kappa B), which suppresses apoptosis by an unknown mechanism. The activation of NF-kappa B was found to block the activation of caspase-8. TRAF1 (TNFR-associated factor 1), TRAF2, and the inhibitor-of-apoptosis (IAP) proteins c-IAP1 and c-IAP2 were identified as gene targets of NF-kappa B transcriptional activity. In cells in which NF-kappa B was inactive, all of these proteins were required to fully suppress TNF-induced apoptosis, whereas c-IAP1 and c-IAP2 were sufficient to suppress etoposide-induced apoptosis. Thus, NF-kappa B activates a group of gene products that function cooperatively at the earliest checkpoint to suppress TNF-alpha -mediated apoptosis and that function more distally to suppress genotoxic agent-mediated apoptosis.

C.-Y. Wang, Department of Endodontics, School of Dentistry, Lineberger Comprehensive Cancer Center, and Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599-7295, USA. M. W. Mayo, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7295, USA. R. G. Korneluk, Molecular Genetics Research Laboratory, Children's Hospital of Eastern Ontario, Ottawa, Ontario K1H 8M5, Canada. D. V. Goeddel, Tularik, 2 Corporate Drive, South San Francisco, CA 94080, USA. A. S. Baldwin Jr., Lineberger Comprehensive Cancer Center, Curriculum in Genetics and Molecular Biology, and Department of Biology, University of North Carolina, Chapel Hill, NC 27599-7295, USA.
*   To whom correspondence should be addressed.

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J. Biol. Chem. 282, 809-820
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Nuclear factor-{kappa}B p65 small interfering RNA or proteasome inhibitor bortezomib sensitizes head and neck squamous cell carcinomas to classic histone deacetylase inhibitors and novel histone deacetylase inhibitor PXD101.
J. Duan, J. Friedman, L. Nottingham, Z. Chen, G. Ara, and C. Van Waes (2007)
Mol. Cancer Ther. 6, 37-50
   Abstract »    Full Text »    PDF »
Parthenolide, a Natural Inhibitor of Nuclear Factor-{kappa}B, Inhibits Lung Colonization of Murine Osteosarcoma Cells.
Y. Kishida, H. Yoshikawa, and A. Myoui (2007)
Clin. Cancer Res. 13, 59-67
   Abstract »    Full Text »    PDF »
Pleiotropic functions of TNF-{alpha} determine distinct IKKbeta-dependent hepatocellular fates in response to LPS.
R. Dajani, S. Sanlioglu, Y. Zhang, Q. Li, M. M. Monick, E. Lazartigues, T. Eggleston, R. L. Davisson, G. W. Hunninghake, and J. F. Engelhardt (2007)
Am J Physiol Gastrointest Liver Physiol 292, G242-G252
   Abstract »    Full Text »    PDF »
Transcriptional Silencing of the Death Gene BNIP3 by Cooperative Action of NF-{kappa}B and Histone Deacetylase 1 in Ventricular Myocytes.
J. Shaw, T. Zhang, M. Rzeszutek, N. Yurkova, D. Baetz, J. R. Davie, and L. A. Kirshenbaum (2006)
Circ. Res. 99, 1347-1354
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A critical role for TNF receptor-associated factor 1 and Bim down-regulation in CD8 memory T cell survival.
L. Sabbagh, C. C. Srokowski, G. Pulle, L. M. Snell, B. J. Sedgmen, Y. Liu, E. N. Tsitsikov, and T. H. Watts (2006)
PNAS 103, 18703-18708
   Abstract »    Full Text »    PDF »
Breast Cancer Metastasis Suppressor 1 Functions as a Corepressor by Enhancing Histone Deacetylase 1-Mediated Deacetylation of RelA/p65 and Promoting Apoptosis.
Y. Liu, P. W. Smith, and D. R. Jones (2006)
Mol. Cell. Biol. 26, 8683-8696
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Cytokines and Chemokines in Uveitis - Is there a Correlation with Clinical Phenotype?.
K. G.-J. Ooi, G. Galatowicz, V. L. Calder, and S. L. Lightman (2006)
Clin. Med. Res. 4, 294-309
   Abstract »    Full Text »    PDF »
Signaling mechanisms underlying metamorphic transitions in animals.
A. Heyland and L. L. Moroz (2006)
Integr. Comp. Biol. 46, 743-759
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VP1686, a Vibrio Type III Secretion Protein, Induces Toll-like Receptor-independent Apoptosis in Macrophage through NF-{kappa}B Inhibition.
R. N. Bhattacharjee, K.-S. Park, Y. Kumagai, K. Okada, M. Yamamoto, S. Uematsu, K. Matsui, H. Kumar, T. Kawai, T. Iida, et al. (2006)
J. Biol. Chem. 281, 36897-36904
   Abstract »    Full Text »    PDF »
NF-{kappa}B inhibition increases chemosensitivity to trichostatin A-induced cell death of Ki-Ras-transformed human prostate epithelial cells.
O. Kwon, K. A Kim, S. O. Kim, R. Ha, W. K. Oh, M. S. Kim, H. S. Kim, G. D. Kim, J. W. Kim, M. Jung, et al. (2006)
Carcinogenesis 27, 2258-2268
   Abstract »    Full Text »    PDF »
Suberoylanilide Hydroxamic Acid Induces Akt-mediated Phosphorylation of p300, Which Promotes Acetylation and Transcriptional Activation of RelA/p65.
Y. Liu, C. E. Denlinger, B. K. Rundall, P. W. Smith, and D. R. Jones (2006)
J. Biol. Chem. 281, 31359-31368
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A Dominant Function of IKK/NF-{kappa}B Signaling in Global Lipopolysaccharide-induced Gene Expression.
N. Carayol, J. Chen, F. Yang, T. Jin, L. Jin, D. States, and C.-Y. Wang (2006)
J. Biol. Chem. 281, 31142-31151
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Differential Inhibition of TRAIL-Mediated DR5-DISC Formation by Decoy Receptors 1 and 2.
D. Merino, N. Lalaoui, A. Morizot, P. Schneider, E. Solary, and O. Micheau (2006)
Mol. Cell. Biol. 26, 7046-7055
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Constitutively Activated Nuclear Factor-{kappa}B, but not Induced NF-{kappa}B, Leads to TRAIL Resistance by Up-Regulation of X-Linked Inhibitor of Apoptosis Protein in Human Cancer Cells.
S. J. Braeuer, C. Buneker, A. Mohr, and R. M. Zwacka (2006)
Mol. Cancer Res. 4, 715-728
   Abstract »    Full Text »    PDF »
The Inhibitor of Apoptosis Protein Fusion c-IAP2{middle dot}MALT1 Stimulates NF-{kappa}B Activation Independently of TRAF1 AND TRAF2.
E. Varfolomeev, S. M. Wayson, V. M. Dixit, W. J. Fairbrother, and D. Vucic (2006)
J. Biol. Chem. 281, 29022-29029
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NF-{kappa}B translocation prevents host cell death after low-dose challenge by Legionella pneumophila.
V. P. Losick and R. R. Isberg (2006)
J. Exp. Med. 203, 2177-2189
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Indirubin Enhances Tumor Necrosis Factor-induced Apoptosis through Modulation of Nuclear Factor-{kappa}B Signaling Pathway.
G. Sethi, K. S. Ahn, S. K. Sandur, X. Lin, M. M. Chaturvedi, and B. B. Aggarwal (2006)
J. Biol. Chem. 281, 23425-23435
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Environmental Tobacco Smoke Suppresses Nuclear Factor-{kappa}B Signaling to Increase Apoptosis in Infant Monkey Lungs.
C.-Y. Zhong, Y. M. Zhou, J. P. Joad, and K. E. Pinkerton (2006)
Am. J. Respir. Crit. Care Med. 174, 428-436
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CD40 Ligation Protects Bronchial Epithelium against Oxidant-Induced Caspase-Independent Cell Death.
A. M. Merendino, F. Bucchieri, R. Gagliardo, A. Daryadel, F. Pompeo, G. Chiappara, R. Santagata, V. Bellia, S. David, F. Farina, et al. (2006)
Am. J. Respir. Cell Mol. Biol. 35, 155-164
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Genetic Deletion of NAD(P)H:Quinone Oxidoreductase 1 Abrogates Activation of Nuclear Factor-{kappa}B, I{kappa}B{alpha} Kinase, c-Jun N-terminal Kinase, Akt, p38, and p44/42 Mitogen-activated Protein Kinases and Potentiates Apoptosis.
K. S. Ahn, G. Sethi, A. K. Jain, A. K. Jaiswal, and B. B. Aggarwal (2006)
J. Biol. Chem. 281, 19798-19808
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Informatics-assisted Protein Profiling in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis.
T. J. Lukas, W. W. Luo, H. Mao, N. Cole, and T. Siddique (2006)
Mol. Cell. Proteomics 5, 1233-1244
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Plumbagin (5-Hydroxy-2-methyl-1,4-naphthoquinone) Suppresses NF-{kappa}B Activation and NF-{kappa}B-regulated Gene Products Through Modulation of p65 and I{kappa}B{alpha} Kinase Activation, Leading to Potentiation of Apoptosis Induced by Cytokine and Chemotherapeutic Agents.
S. K. Sandur, H. Ichikawa, G. Sethi, K. S. Ahn, and B. B. Aggarwal (2006)
J. Biol. Chem. 281, 17023-17033
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Integrin-Mediated Transcriptional Activation of Inhibitor of Apoptosis Proteins Protects Smooth Muscle Cells Against Apoptosis Induced by Degraded Collagen.
K. von Wnuck Lipinski, P. Keul, N. Ferri, S. Lucke, G. Heusch, J. W. Fischer, and B. Levkau (2006)
Circ. Res. 98, 1490-1497
   Abstract »    Full Text »    PDF »


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