This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wang, Y.
Right arrow Articles by Chin, Y. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, Y.
Right arrow Articles by Chin, Y. E.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 2000, p. 4505-4512, Vol. 20, No. 13
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Stat1 as a Component of Tumor Necrosis Factor Alpha Receptor 1-TRADD Signaling Complex To Inhibit NF-kappa B Activation

Yingjian Wang,1 Tong R. Wu,2 Shiying Cai,1 Thomas Welte,1 and Y. Eugene Chin1,*

Department of Pathology and Laboratory Medicine, Brown University School of Medicine, Providence, Rhode Island 02912,2 and Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 065101

Received 14 October 1999/Returned for modification 17 November 1999/Accepted 15 March 2000

Activated tumor necrosis factor alpha (TNF-alpha ) receptor 1 (TNFR1) recruits TNFR1-associated death domain protein (TRADD), which in turn triggers two opposite signaling pathways leading to caspase activation for apoptosis induction and NF-kappa B activation for antiapoptosis gene upregulation. Here we show that Stat1 is involved in the TNFR1-TRADD signaling complex, as determined by employing a novel antibody array screening method. In HeLa cells, Stat1 was associated with TNFR1 and this association was increased with TNF-alpha treatment. TNFR1 signaling factors TRADD and Fas-associated death domain protein (FADD) were also found to interact with Stat1 in a TNF-alpha -dependent process. Our in vitro recombinant protein-protein interaction studies demonstrated that Stat1 could directly interact with TNFR1 and TRADD but not with FADD. Interaction between Stat1 and receptor-interacting protein (RIP) or TNFR-associated factor 2 (TRAF2) was not detected. Examination of Stat1-deficient cells showed an apparent increase in TNF-alpha -induced TRADD-RIP and TRADD-TRAF2 complex formation, while interaction between TRADD and FADD was unaffected. As a consequence, TNF-alpha -mediated I-kappa B degradation and NF-kappa B activation were markedly enhanced in Stat1-deficient cells, whereas overexpression of Stat1 in 293T cells blocked NF-kappa B activation by TNF-alpha . Thus, Stat1 acts as a TNFR1-signaling molecule to suppress NF-kappa B activation.

* Corresponding author. Mailing address: Department of Pathology and Laboratory Medicine, Brown University School of Medicine, Providence, RI 02912. Phone: (401) 863-2540. Fax: (401) 863-9008. E-mail: Y_Eugene_Chin{at}Brown.edu.

Molecular and Cellular Biology, July 2000, p. 4505-4512, Vol. 20, No. 13
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Tliba, O., Amrani, Y. (2008). Airway Smooth Muscle Cell as an Inflammatory Cell: Lessons Learned from Interferon Signaling Pathways. Proc Am Thorac Soc 5: 106-112 [Abstract] [Full Text]  
  • Smith, M. A., Moylan, J. S., Smith, J. D., Li, W., Reid, M. B. (2007). IFN-{gamma} does not mimic the catabolic effects of TNF-{alpha}. Am. J. Physiol. Cell Physiol. 293: C1947-C1952 [Abstract] [Full Text]  
  • Hayashi, T., Ishida, Y., Kimura, A., Iwakura, Y., Mukaida, N., Kondo, T. (2007). IFN-{gamma} Protects Cerulein-Induced Acute Pancreatitis by Repressing NF-{kappa}B Activation. J. Immunol. 178: 7385-7394 [Abstract] [Full Text]  
  • Lui, V. W. Y., Boehm, A. L., Koppikar, P., Leeman, R. J., Johnson, D., Ogagan, M., Childs, E., Freilino, M., Grandis, J. R. (2007). Antiproliferative Mechanisms of a Transcription Factor Decoy Targeting Signal Transducer and Activator of Transcription (STAT) 3: The Role of STAT1. Mol. Pharmacol. 71: 1435-1443 [Abstract] [Full Text]  
  • Keslacy, S., Tliba, O., Baidouri, H., Amrani, Y. (2007). Inhibition of Tumor Necrosis Factor-{alpha}-Inducible Inflammatory Genes by Interferon-{gamma} Is Associated with Altered Nuclear Factor-{kappa}B Transactivation and Enhanced Histone Deacetylase Activity. Mol. Pharmacol. 71: 609-618 [Abstract] [Full Text]  
  • Longman, R. S., Braun, D., Pellegrini, S., Rice, C. M., Darnell, R. B., Albert, M. L. (2007). Dendritic-cell maturation alters intracellular signaling networks, enabling differential effects of IFN-{alpha}/{beta} on antigen cross-presentation. Blood 109: 1113-1122 [Abstract] [Full Text]  
  • Bharhani, M. S., Borojevic, R., Basak, S., Ho, E., Zhou, P., Croitoru, K. (2006). IL-10 protects mouse intestinal epithelial cells from Fas-induced apoptosis via modulating Fas expression and altering caspase-8 and FLIP expression.. Am. J. Physiol. Gastrointest. Liver Physiol. 291: G820-G829 [Abstract] [Full Text]  
  • He, Y., Zhang, W., Zhang, R., Zhang, H., Min, W. (2006). SOCS1 Inhibits Tumor Necrosis Factor-induced Activation of ASK1-JNK Inflammatory Signaling by Mediating ASK1 Degradation. J. Biol. Chem. 281: 5559-5566 [Abstract] [Full Text]  
  • Kramer, O. H., Baus, D., Knauer, S. K., Stein, S., Jager, E., Stauber, R. H., Grez, M., Pfitzner, E., Heinzel, T. (2006). Acetylation of Stat1 modulates NF-{kappa}B activity.. Genes Dev. 20: 473-485 [Abstract] [Full Text]  
  • Chen, J.-T., Liang, J.-B., Chou, C.-L., Chien, M.-W., Shyu, R.-C., Chou, P.-I, Lu, D.-W. (2006). Glucosamine Sulfate Inhibits TNF-{alpha} and IFN-{gamma}-Induced Production of ICAM-1 in Human Retinal Pigment Epithelial Cells In Vitro. IOVS 47: 664-672 [Abstract] [Full Text]  
  • Kim, H. S., Lee, M.-S. (2005). Essential Role of STAT1 in Caspase-Independent Cell Death of Activated Macrophages through the p38 Mitogen-Activated Protein Kinase/STAT1/Reactive Oxygen Species Pathway. Mol. Cell. Biol. 25: 6821-6833 [Abstract] [Full Text]  
  • Chung, A. S., Guan, Y.-j., Yuan, Z.-L., Albina, J. E., Chin, Y. E. (2005). Ankyrin Repeat and SOCS Box 3 (ASB3) Mediates Ubiquitination and Degradation of Tumor Necrosis Factor Receptor II. Mol. Cell. Biol. 25: 4716-4726 [Abstract] [Full Text]  
  • Cousens, L. P., Goulette, F. A., Darnowski, J. W. (2005). JAK-Mediated Signaling Inhibits Fas Ligand-Induced Apoptosis Independent of De Novo Protein Synthesis. J. Immunol. 174: 320-327 [Abstract] [Full Text]  
  • Thomas, M., Finnegan, C. E., Rogers, K. M.-A., Purcell, J. W., Trimble, A., Johnston, P. G., Boland, M. P. (2004). STAT1: A Modulator of Chemotherapy-induced Apoptosis. Cancer Res. 64: 8357-8364 [Abstract] [Full Text]  
  • Yuan, Z.-l., Guan, Y.-j., Wang, L., Wei, W., Kane, A. B., Chin, Y. E. (2004). Central Role of the Threonine Residue within the p+1 Loop of Receptor Tyrosine Kinase in STAT3 Constitutive Phosphorylation in Metastatic Cancer Cells. Mol. Cell. Biol. 24: 9390-9400 [Abstract] [Full Text]  
  • Baran-Marszak, F., Feuillard, J., Najjar, I., Le Clorennec, C., Bechet, J.-M., Dusanter-Fourt, I., Bornkamm, G. W., Raphael, M., Fagard, R. (2004). Differential roles of STAT1{alpha} and STAT1{beta} in fludarabine-induced cell cycle arrest and apoptosis in human B cells. Blood 104: 2475-2483 [Abstract] [Full Text]  
  • Ferreira, C. V., Bos, C. L., Versteeg, H. H., Justo, G. Z., Duran, N., Peppelenbosch, M. P. (2004). Molecular mechanism of violacein-mediated human leukemia cell death. Blood 104: 1459-1464 [Abstract] [Full Text]  
  • Ivanov, S. S., Chung, A. S., Yuan, Z.-l., Guan, Y.-j., Sachs, K. V., Reichner, J. S., Chin, Y. E. (2004). Antibodies Immobilized as Arrays to Profile Protein Post-translational Modifications in Mammalian Cells. Mol. Cell. Proteomics 3: 788-795 [Abstract] [Full Text]  
  • Marques, L., Brucet, M., Lloberas, J., Celada, A. (2004). STAT1 Regulates Lipopolysaccharide- and TNF-{alpha}-Dependent Expression of Transporter Associated with Antigen Processing 1 and Low Molecular Mass Polypeptide 2 Genes in Macrophages by Distinct Mechanisms. J. Immunol. 173: 1103-1110 [Abstract] [Full Text]  
  • Gao, Q., Hua, J., Kimura, R., Headd, J. J., Fu, X.-y., Chin, Y. E. (2004). Identification of the Linker-SH2 Domain of STAT as the Origin of the SH2 Domain Using Two-dimensional Structural Alignment. Mol. Cell. Proteomics 3: 704-714 [Abstract] [Full Text]  
  • Kimura, A., Naka, T., Nagata, S., Kawase, I., Kishimoto, T. (2004). SOCS-1 suppresses TNF-{alpha}-induced apoptosis through the regulation of Jak activation. Int Immunol 16: 991-999 [Abstract] [Full Text]  
  • Tliba, O., Tliba, S., Da Huang, C., Hoffman, R. K., DeLong, P., Panettieri, R. A. Jr., Amrani, Y. (2003). Tumor Necrosis Factor {alpha} Modulates Airway Smooth Muscle Function via the Autocrine Action of Interferon {beta}. J. Biol. Chem. 278: 50615-50623 [Abstract] [Full Text]  
  • Choi, D.-S., Young, H., McMahon, T., Wang, D., Messing, R. O. (2003). The Mouse RACK1 Gene Is Regulated by Nuclear Factor-{kappa}B and Contributes to Cell Survival. Mol. Pharmacol. 64: 1541-1548 [Abstract] [Full Text]  
  • Wesemann, D. R., Benveniste, E. N. (2003). STAT-1{alpha} and IFN-{gamma} as Modulators of TNF-{alpha} Signaling in Macrophages: Regulation and Functional Implications of the TNF Receptor 1:STAT-1{alpha} Complex. J. Immunol. 171: 5313-5319 [Abstract] [Full Text]  
  • Battle, T. E., Wierda, W. G., Rassenti, L. Z., Zahrieh, D., Neuberg, D., Kipps, T. J., Frank, D. A. (2003). In Vivo Activation of Signal Transducer and Activator of Transcription 1 after CD154 Gene Therapy for Chronic Lymphocytic Leukemia Is Associated with Clinical and Immunologic Response. Clin. Cancer Res. 9: 2166-2172 [Abstract] [Full Text]  
  • Ashton, A. W., Ware, G. M., Kaul, D. K., Ware, J. A. (2003). Inhibition of Tumor Necrosis Factor alpha -mediated NFkappa B Activation and Leukocyte Adhesion, with Enhanced Endothelial Apoptosis, by G Protein-linked Receptor (TP) Ligands. J. Biol. Chem. 278: 11858-11866 [Abstract] [Full Text]  
  • Wu, T. R., Hong, Y. K., Wang, X.-D., Ling, M. Y., Dragoi, A. M., Chung, A. S., Campbell, A. G., Han, Z.-Y., Feng, G.-S., Chin, Y. E. (2002). SHP-2 Is a Dual-specificity Phosphatase Involved in Stat1 Dephosphorylation at Both Tyrosine and Serine Residues in Nuclei. J. Biol. Chem. 277: 47572-47580 [Abstract] [Full Text]  
  • Nguyen, K. B., Watford, W. T., Salomon, R., Hofmann, S. R., Pien, G. C., Morinobu, A., Gadina, M., O'Shea, J. J., Biron, C. A. (2002). Critical Role for STAT4 Activation by Type 1 Interferons in the Interferon-gamma Response to Viral Infection. Science 297: 2063-2066 [Abstract] [Full Text]  
  • Schreiber, S, Rosenstiel, P, Hampe, J, Nikolaus, S, Groessner, B, Schottelius, A, Kuhbacher, T, Hamling, J, Folsch, U R, Seegert, D (2002). Activation of signal transducer and activator of transcription (STAT) 1 in human chronic inflammatory bowel disease. Gut 51: 379-385 [Abstract] [Full Text]  
  • Wesemann, D. R., Dong, Y., O'Keefe, G. M., Nguyen, V. T., Benveniste, E. N. (2002). Suppressor of Cytokine Signaling 1 Inhibits Cytokine Induction of CD40 Expression in Macrophages. J. Immunol. 169: 2354-2360 [Abstract] [Full Text]  
  • Xia, L., Wang, L., Chung, A. S., Ivanov, S. S., Ling, M. Y., Dragoi, A. M., Platt, A., Gilmer, T. M., Fu, X.-Y., Chin, Y. E. (2002). Identification of Both Positive and Negative Domains within the Epidermal Growth Factor Receptor COOH-terminal Region for Signal Transducer and Activator of Transcription (STAT) Activation. J. Biol. Chem. 277: 30716-30723 [Abstract] [Full Text]  
  • Cottet, S., Dupraz, P., Hamburger, F., Dolci, W., Jaquet, M., Thorens, B. (2002). cFLIP Protein Prevents Tumor Necrosis Factor-{alpha}-Mediated Induction of Caspase-8-Dependent Apoptosis in Insulin-Secreting {beta}Tc-Tet Cells. Diabetes 51: 1805-1814 [Abstract] [Full Text]  
  • Durbin, J. E., Johnson, T. R., Durbin, R. K., Mertz, S. E., Morotti, R. A., Peebles, R. S., Graham, B. S. (2002). The Role of IFN in Respiratory Syncytial Virus Pathogenesis. J. Immunol. 168: 2944-2952 [Abstract] [Full Text]  
  • Kim, H., Lee, T.-H., Hwang, Y. S., Bang, M. A., Kim, K. H., Suh, J. M., Chung, H. K., Yu, D.-Y., Lee, K.-K., Kwon, O-Y., Ro, H. K., Shong, M. (2001). Methimazole As an Antioxidant and Immunomodulator in Thyroid Cells: Mechanisms Involving Interferon-gamma Signaling and H2O2 Scavenging. Mol. Pharmacol. 60: 972-980 [Abstract] [Full Text]  
  • Zhu, Y. K., Liu, X. D., Skold, M. C., Umino, T., Wang, H., Romberger, D. J., Spurzem, J. R., Kohyama, T., Wen, F.-Q., Rennard, S. I. (2001). Cytokine Inhibition of Fibroblast-Induced Gel Contraction Is Mediated by PGE2 and NO Acting Through Separate Parallel Pathways. Am. J. Respir. Cell Mol. Bio. 25: 245-253 [Abstract] [Full Text]  
  • Ganster, R. W., Taylor, B. S., Shao, L., Geller, D. A. (2001). Complex regulation of human inducible nitric oxide synthase gene transcription by Stat 1 and NF-kappa B. Proc. Natl. Acad. Sci. USA 10.1073/pnas.151239498v1 [Abstract] [Full Text]  
  • Sahni, M., Raz, R., Coffin, J. D., Levy, D., Basilico, C. (2001). STAT1 mediates the increased apoptosis and reduced chondrocyte proliferation in mice overexpressing FGF2. Development 128: 2119-2129 [Abstract] [Full Text]  
  • LANGEN, R. C. J., SCHOLS, A. M. W. J., KELDERS, M. C. J. M., WOUTERS, E. F. M., JANSSEN-HEININGER, Y. M. W. (2001). Inflammatory cytokines inhibit myogenic differentiation through activation of nuclear factor-{kappa}B. FASEB J. 15: 1169-1180 [Abstract] [Full Text]  
  • Ganster, R. W., Taylor, B. S., Shao, L., Geller, D. A. (2001). Complex regulation of human inducible nitric oxide synthase gene transcription by Stat 1 and NF-kappa B. Proc. Natl. Acad. Sci. USA 98: 8638-8643 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»