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Tumor necrosis factor (TNF) is a major mediator of
apoptosis as well as inflammation and immunity, and it has been
implicatedin the pathogenesis of a wide spectrum of human diseases,
includingsepsis, diabetes, cancer, osteoporosis, multiple sclerosis,
rheumatoidarthritis, and inflammatory bowel diseases. The interaction
ofTNF with TNF receptor-1 (TNF-R1) activates several signal
transductionpathways. A common feature of each pathway is the
TNF-inducedformation of a multiprotein signaling complex at the cell
membrane.Over the past decade, many of the components and mechanisms
ofthese signaling pathways have been elucidated. We provide an
overviewof current knowledge of TNF signaling and introduce an STKE
ConnectionsMap that depicts a canonical view of this process.
Tularik Inc., Two Corporate Drive, South San Francisco, CA 94080, USA.
*
To whom correspondence should be addressed. E-mail:
goeddel{at}tularik.com
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T. So, P. Soroosh, S.-Y. Eun, A. Altman, and M. Croft (2011)
PNAS
108, 2903-2908
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M. Yu, J. Lam, B. Rada, T. L. Leto, and S. J. Levine (2011)
J. Immunol.
186, 1180-1188
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J. A. Bristol, A. R. Robinson, E. A. Barlow, and S. C. Kenney (2010)
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C. Salaun, C. Leroy, A. Rousseau, V. Boitez, L. Beck, and G. Friedlander (2010)
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J. W. Bartsch, D. Wildeboer, G. Koller, S. Naus, A. Rittger, M. L. Moss, Y. Minai, and H. Jockusch (2010)
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RSK2 mediates NF-{kappa}B activity through the phosphorylation of I{kappa}B{alpha} in the TNF-R1 pathway.
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Concerted action of wild-type and mutant TNF receptors enhances inflammation in TNF receptor 1-associated periodic fever syndrome.
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M. Noti, N. Corazza, G. Tuffin, K. Schoonjans, and T. Brunner (2010)
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Tumor Necrosis Factor {alpha} Represses Bone Morphogenetic Protein (BMP) Signaling by Interfering with the DNA Binding of Smads through the Activation of NF-{kappa}B.
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Leukocyte Ig-like Receptor B4 (LILRB4) Is a Potent Inhibitor of Fc{gamma}RI-mediated Monocyte Activation via Dephosphorylation of Multiple Kinases.
H. K. Lu, C. Rentero, M. J. Raftery, L. Borges, K. Bryant, and N. Tedla (2009)
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Crosstalk in Inflammation: The Interplay of Glucocorticoid Receptor-Based Mechanisms and Kinases and Phosphatases.
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Bcl3 Interacts Cooperatively with Peroxisome Proliferator-Activated Receptor Gamma (PPAR{gamma}) Coactivator 1{alpha} To Coactivate Nuclear Receptors Estrogen-Related Receptor {alpha} and PPAR{alpha}.
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PRMT5, a Novel TRAIL Receptor-Binding Protein, Inhibits TRAIL-Induced Apoptosis via Nuclear Factor-{kappa}B Activation.
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Cannabinoid Receptor Activation Induces Apoptosis through Tumor Necrosis Factor {alpha}-Mediated Ceramide De novo Synthesis in Colon Cancer Cells.
F. Cianchi, L. Papucci, N. Schiavone, M. Lulli, L. Magnelli, M. C. Vinci, L. Messerini, C. Manera, E. Ronconi, P. Romagnani, et al. (2008)
Clin. Cancer Res.
14, 7691-7700
|Abstract »|Full Text »|PDF »
Parkin Deficiency Increases Vulnerability to Inflammation-Related Nigral Degeneration.
T. C. Frank-Cannon, T. Tran, K. A. Ruhn, T. N. Martinez, J. Hong, M. Marvin, M. Hartley, I. Trevino, D. E. O'Brien, B. Casey, et al. (2008)
J. Neurosci.
28, 10825-10834
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The Interaction between Human Papillomavirus Type 16 and FADD Is Mediated by a Novel E6 Binding Domain.
S. S. Tungteakkhun, M. Filippova, J. W. Neidigh, N. Fodor, and P. J. Duerksen-Hughes (2008)
J. Virol.
82, 9600-9614
|Abstract »|Full Text »|PDF »
Role of NF-{kappa}B and PI 3-kinase/Akt in TNF-{alpha}-induced cytotoxicity in microvascular endothelial cells.
Z. Zhou, P. Gengaro, W. Wang, X.-q. Wang, C. Li, S. Faubel, C. Rivard, and R. W. Schrier (2008)
Am J Physiol Renal Physiol
295, F932-F941
|Abstract »|Full Text »|PDF »
Functional genetic screening reveals the role of mitochondrial cytochrome b as a mediator of FAS-induced apoptosis.
A. P. Komarov, O. W. Rokhlin, C.-A. Yu, and A. V. Gudkov (2008)
PNAS
105, 14453-14458
|Abstract »|Full Text »|PDF »
cAMP-dependent Protein Kinase A (PKA) Signaling Induces TNFR1 Exosome-like Vesicle Release via Anchoring of PKA Regulatory Subunit RII{beta} to BIG2.
A. Islam, H. Jones, T. Hiroi, J. Lam, J. Zhang, J. Moss, M. Vaughan, and S. J. Levine (2008)
J. Biol. Chem.
283, 25364-25371
|Abstract »|Full Text »|PDF »
c-IAP1 and c-IAP2 Are Critical Mediators of Tumor Necrosis Factor {alpha} (TNF{alpha})-induced NF-{kappa}B Activation.
E. Varfolomeev, T. Goncharov, A. V. Fedorova, J. N. Dynek, K. Zobel, K. Deshayes, W. J. Fairbrother, and D. Vucic (2008)
J. Biol. Chem.
283, 24295-24299
|Abstract »|Full Text »|PDF »
Beyond tumor necrosis factor receptor: TRADD signaling in toll-like receptors.
N.-J. Chen, I. I. C. Chio, W.-J. Lin, G. Duncan, H. Chau, D. Katz, H.-L. Huang, K. A. Pike, Z. Hao, Y.-W. Su, et al. (2008)
PNAS
105, 12429-12434
|Abstract »|Full Text »|PDF »
Diesel exhaust particles induce oxidative stress, proinflammatory signaling, and P-glycoprotein up-regulation at the blood-brain barrier.
A. M. S. Hartz, B. Bauer, M. L. Block, J.-S. Hong, and D. S. Miller (2008)
FASEB J
22, 2723-2733
|Abstract »|Full Text »|PDF »
Essential Cytoplasmic Translocation of a Cytokine Receptor-Assembled Signaling Complex.
A. Matsuzawa, P.-H. Tseng, S. Vallabhapurapu, J.-L. Luo, W. Zhang, H. Wang, D. A. A. Vignali, E. Gallagher, and M. Karin (2008)
Science
321, 663-668
|Abstract »|Full Text »|PDF »
Abrogation of Anti-Inflammatory Transcription Factor LKLF in Neutrophil-Dominated Airways.
M. T. Saavedra, A. D. Patterson, J. West, S. H. Randell, D. W. Riches, K. C. Malcolm, C. D. Cool, J. A. Nick, and C. A. Dinarello (2008) 38, 679-688
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Uniocular Anterior Chamber Inoculation of a Tumor Necrosis Factor Alpha-Expressing Recombinant of Herpes Simplex Virus Type 1 Results in More Rapid Destruction and Increased Viral Replication in the Retina of the Uninoculated Eye.
M. A. Fields, M. Zheng, P. Wall, S. Oberg, and S. S. Atherton (2008)
J. Virol.
82, 5068-5078
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Desflurane Preconditioning Inhibits Endothelial Nuclear Factor-{kappa}-B Activation by Targeting the Proximal End of Tumor Necrosis Factor-{alpha} Signaling.
Simvastatin antagonizes tumor necrosis factor-{alpha} inhibition of bone morphogenetic proteins-2-induced osteoblast differentiation by regulating Smad signaling and Ras/Rho-mitogen-activated protein kinase pathway.
M. Yamashita, F. Otsuka, T. Mukai, H. Otani, K. Inagaki, T. Miyoshi, J. Goto, M. Yamamura, and H. Makino (2008)
J. Endocrinol.
196, 601-613
|Abstract »|Full Text »|PDF »
Transglutaminase Type II Is Involved in the Pathogenesis of Endotoxic Shock.
L. Falasca, M. G. Farrace, A. Rinaldi, L. Tuosto, G. Melino, and M. Piacentini (2008)
J. Immunol.
180, 2616-2624
|Abstract »|Full Text »|PDF »
Aberrant activation of stress-response pathways leads to TNF-{alpha} oversecretion in Fanconi anemia.
D. Briot, G. Mace-Aime, F. Subra, and F. Rosselli (2008)
Blood
111, 1913-1923
|Abstract »|Full Text »|PDF »
Creation and X-ray Structure Analysis of the Tumor Necrosis Factor Receptor-1-selective Mutant of a Tumor Necrosis Factor-{alpha} Antagonist.
H. Shibata, Y. Yoshioka, A. Ohkawa, K. Minowa, Y. Mukai, Y. Abe, M. Taniai, T. Nomura, H. Kayamuro, H. Nabeshi, et al. (2008)
J. Biol. Chem.
283, 998-1007
|Abstract »|Full Text »|PDF »
Activation of Rho Kinase by TNF-{alpha} Is Required for JNK Activation in Human Pulmonary Microvascular Endothelial Cells.
P. Y. Mong, C. Petrulio, H. L. Kaufman, and Q. Wang (2008)
J. Immunol.
180, 550-558
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FOXO3a Turns the Tumor Necrosis Factor Receptor Signaling Towards Apoptosis Through Reciprocal Regulation of c-Jun N-Terminal Kinase and NF-{kappa}B.
H.-Y. Lee, S.-W. Youn, J.-Y. Kim, K.-W. Park, C.-I. Hwang, W.-Y. Park, B.-H. Oh, Y.-B. Park, K. Walsh, J.-S. Seo, et al. (2008)
Arterioscler Thromb Vasc Biol
28, 112-120
|Abstract »|Full Text »|PDF »
Differential activation of the death receptor pathway in human target cells induced by cytotoxic T lymphocytes showing different kinetics of killing.
J. F. de Vries, P. A. von dem Borne, S. A.P. van Luxemburg-Heijs, M. H.M. Heemskerk, R. Willemze, J.H. F. Falkenburg, and R. M.Y. Barge (2007)
Haematologica
92, 1671-1678
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Tumor Necrosis Factor-{alpha} Augments Matrix Metalloproteinase-9 Production in Skeletal Muscle Cells through the Activation of Transforming Growth Factor- -activated Kinase 1 (TAK1)-dependent Signaling Pathway.
A. K. Srivastava, X. Qin, N. Wedhas, M. Arnush, T. A. Linkhart, R. B. Chadwick, and A. Kumar (2007)
J. Biol. Chem.
282, 35113-35124
|Abstract »|Full Text »|PDF »
Menin-mediated Caspase 8 Expression in Suppressing Multiple Endocrine Neoplasia Type 1.
P. La, Y. Yang, S. K. Karnik, A. C. Silva, R. W. Schnepp, S. K. Kim, and X. Hua (2007)
J. Biol. Chem.
282, 31332-31340
|Abstract »|Full Text »|PDF »
The Importance of Myeloid-Derived Suppressor Cells in the Regulation of Autoimmune Effector Cells by a Chronic Contact Eczema.
R. Marhaba, M. Vitacolonna, D. Hildebrand, M. Baniyash, P. Freyschmidt-Paul, and M. Zoller (2007)
J. Immunol.
179, 5071-5081
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