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Science 296 (5573): 1634-1635

Copyright © 2002 by the American Association for the Advancement of Science

TNF-R1 Signaling: A Beautiful Pathway

Guoqing Chen, David V. Goeddel*

Tumor necrosis factor (TNF) is a major mediator of apoptosis as well as inflammation and immunity, and it has been implicated in the pathogenesis of a wide spectrum of human diseases, including sepsis, diabetes, cancer, osteoporosis, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel diseases. The interaction of TNF with TNF receptor-1 (TNF-R1) activates several signal transduction pathways. A common feature of each pathway is the TNF-induced formation of a multiprotein signaling complex at the cell membrane. Over the past decade, many of the components and mechanisms of these signaling pathways have been elucidated. We provide an overview of current knowledge of TNF signaling and introduce an STKE Connections Map 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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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}.
J. Yang, R. S. Williams, and D. P. Kelly (2009)
Mol. Cell. Biol. 29, 4091-4102
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Kidney ischemia-reperfusion injury induces caspase-dependent pulmonary apoptosis.
H. T. Hassoun, M. L. Lie, D. N. Grigoryev, M. Liu, R. M. Tuder, and H. Rabb (2009)
Am J Physiol Renal Physiol 297, F125-F137
   Abstract »    Full Text »    PDF »
WISP1, a Pro-mitogenic, Pro-survival Factor, Mediates Tumor Necrosis Factor-{alpha} (TNF-{alpha})-stimulated Cardiac Fibroblast Proliferation but Inhibits TNF-{alpha}-induced Cardiomyocyte Death.
K. Venkatachalam, B. Venkatesan, A. J. Valente, P. C. Melby, S. Nandish, J. E. B. Reusch, R. A. Clark, and B. Chandrasekar (2009)
J. Biol. Chem. 284, 14414-14427
   Abstract »    Full Text »    PDF »
PRMT5, a Novel TRAIL Receptor-Binding Protein, Inhibits TRAIL-Induced Apoptosis via Nuclear Factor-{kappa}B Activation.
H. Tanaka, Y. Hoshikawa, T. Oh-hara, S. Koike, M. Naito, T. Noda, H. Arai, T. Tsuruo, and N. Fujita (2009)
Mol. Cancer Res. 7, 557-569
   Abstract »    Full Text »    PDF »
Poxvirus MC160 Protein Utilizes Multiple Mechanisms To Inhibit NF-{kappa}B Activation Mediated via Components of the Tumor Necrosis Factor Receptor 1 Signal Transduction Pathway.
D. B. Nichols and J. L. Shisler (2009)
J. Virol. 83, 3162-3174
   Abstract »    Full Text »    PDF »
ROS and Innate Immunity.
C. KOHCHI, H. INAGAWA, T. NISHIZAWA, and G.-I. SOMA (2009)
Anticancer Res 29, 817-821
   Abstract »    Full Text »    PDF »
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
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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
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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 »
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
   Abstract »    Full Text »    PDF »
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 »
Dissecting "stress" in Fanconi anemia.
I. Dokal (2008)
Blood 111, 1756-1757
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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
   Abstract »    Full Text »    PDF »

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