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Science 28 November 1997:
Vol. 278. no. 5343, pp. 1630 - 1632
DOI: 10.1126/science.278.5343.1630
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Reports

Defective TNF-alpha -Induced Apoptosis in STAT1-Null Cells Due to Low Constitutive Levels of Caspases

Aseem Kumar, * Mairead Commane, Thomas W. Flickinger, Curt M. Horvath, George R. Stark dagger

Signal transducers and activators of transcription (STATs) enhance transcription of specific genes in response to cytokines and growth factors. STAT1 is also required for efficient constitutive expression of the caspases Ice, Cpp32, and Ich-1 in human fibroblasts. As a consequence, STAT1-null cells are resistant to apoptosis by tumor necrosis factor alpha  (TNF-alpha ). Reintroduction of STAT1alpha restored both TNF-alpha -induced apoptosis and the expression of Ice, Cpp32, and Ich-1. Variant STAT1 proteins carrying point mutations that inactivate domains required for STAT dimer formation nevertheless restored protease expression and sensitivity to apoptosis, indicating that the functions of STAT1 required for these activities are different from those that mediate induced gene expression.

A. Kumar, M. Commane, T. W. Flickinger, G. R. Stark, Department of Molecular Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
C. M. Horvath, Laboratory of Molecular Cell Biology, The Rockefeller University, New York, NY 10021, USA.
*   Present address: Sections of Cardiology and Critical Care Medicine, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA.

dagger    To whom correspondence should be addressed. E-mail: starkg{at}cesmtp.ccf.org

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   Abstract »    Full Text »    PDF »
Stat5B Shuttles Between Cytoplasm and Nucleus in a Cytokine-Dependent and -Independent Manner.
R. Zeng, Y. Aoki, M. Yoshida, K.-i. Arai, and S. Watanabe (2002)
J. Immunol. 168, 4567-4575
   Abstract »    Full Text »    PDF »
Stat1-Dependent, p53-Independent Expression of p21waf1 Modulates Oxysterol-Induced Apoptosis.
S. Agrawal, M. L. Agarwal, M. Chatterjee-Kishore, G. R. Stark, and G. M. Chisolm (2002)
Mol. Cell. Biol. 22, 1981-1992
   Abstract »    Full Text »    PDF »
Roles of Stat1, Stat2, and Interferon Regulatory Factor-9 (IRF-9) in Interferon Tau Regulation of IRF-1.
M. D. Stewart, Y. Choi, G. A. Johnson, L.-y. Yu-Lee, F. W. Bazer, and T. E. Spencer (2002)
Biol Reprod 66, 393-400
   Abstract »    Full Text »    PDF »
Molecular Cross-talk between the TRAIL and Interferon Signaling Pathways.
C. Kumar-Sinha, S. Varambally, A. Sreekumar, and A. M. Chinnaiyan (2002)
J. Biol. Chem. 277, 575-585
   Abstract »    Full Text »
Longer and Shorter Forms of Sendai Virus C Proteins Play Different Roles in Modulating the Cellular Antiviral Response.
D. Garcin, J. Curran, M. Itoh, and D. Kolakofsky (2001)
J. Virol. 75, 6800-6807
   Abstract »    Full Text »
Dissection of the Intracellular Pathways in Hepatocytes Suggests a Role for Jun Kinase and IFN Regulatory Factor-1 in Con A-Induced Liver Failure.
K. Streetz, B. Fregien, J. Plumpe, K. Korber, S. Kubicka, G. Sass, S. C. Bischoff, M. P. Manns, G. Tiegs, and C. Trautwein (2001)
J. Immunol. 167, 514-523
   Abstract »    Full Text »    PDF »
STAT1 mediates the increased apoptosis and reduced chondrocyte proliferation in mice overexpressing FGF2.
M. Sahni, R. Raz, J. D. Coffin, D. Levy, and C. Basilico (2001)
Development 128, 2119-2129
   Abstract »    Full Text »    PDF »
The SH Integral Membrane Protein of the Paramyxovirus Simian Virus 5 Is Required To Block Apoptosis in MDBK Cells.
B. He, G. Y. Lin, J. E. Durbin, R. K. Durbin, and R. A. Lamb (2001)
J. Virol. 75, 4068-4079
   Abstract »    Full Text »
Interferon-{{tau}} (IFN{{tau}}) Regulation of IFN-Stimulated Gene Expression in Cell Lines Lacking Specific IFN-Signaling Components.
M. D. Stewart, G. A. Johnson, F. W. Bazer, and T. E. Spencer (2001)
Endocrinology 142, 1786-1794
   Abstract »    Full Text »
IFN-{{gamma}}/TNF-{{alpha}} Synergism as the Final Effector in Autoimmune Diabetes: A Key Role for STAT1/IFN Regulatory Factor-1 Pathway in Pancreatic {{beta}} Cell Death.
K. Suk, S. Kim, Y.-H. Kim, K.-A. Kim, I. Chang, H. Yagita, M. Shong, and M.-S. Lee (2001)
J. Immunol. 166, 4481-4489
   Abstract »    Full Text »    PDF »
Constitutively activated Stat3 protects fibroblasts from serum withdrawal and UV-induced apoptosis and antagonizes the proapoptotic effects of activated Stat1.
Y. Shen, G. Devgan, J. E. Darnell Jr., and J. F. Bromberg (2001)
PNAS
   Abstract »    Full Text »
Sendai Virus C Proteins Must Interact Directly with Cellular Components To Interfere with Interferon Action.
D. Garcin, J. Curran, and D. Kolakofsky (2000)
J. Virol. 74, 8823-8830
   Abstract »    Full Text »
Expression of Protein Mediators of Type I Interferon Signaling in Human Squamous Cell Carcinoma of the Skin.
J. L. Clifford, D. G. Menter, X. Yang, E. Walch, C. Zou, G. L. Clayman, T. S. Schaefer, A. K. El-Naggar, R. Lotan, and S. M. Lippman (2000)
Cancer Epidemiol. Biomarkers Prev. 9, 993-997
   Abstract »    Full Text »
Fas- and Interferon {gamma}-Induced Apoptosis in Chang Conjunctival Cells: Further Investigations.
M. D. S. Jean, C. Debbasch, M. Rahmani, F. Brignole, G. Feldmann, J.-M. Warnet, and C. Baudouin (2000)
Invest. Ophthalmol. Vis. Sci. 41, 2531-2543
   Abstract »    Full Text »
Stat1 as a Component of Tumor Necrosis Factor Alpha Receptor 1-TRADD Signaling Complex To Inhibit NF-kappa B Activation.
Y. Wang, T. R. Wu, S. Cai, T. Welte, and Y. E. Chin (2000)
Mol. Cell. Biol. 20, 4505-4512
   Abstract »    Full Text »
Distinct roles of the NH2- and COOH-terminal domains of the protein inhibitor of activated signal transducer and activator of transcription (STAT) 1 (PIAS1) in cytokine-induced PIAS1-Stat1 interaction.
J. Liao, Y. Fu, and K. Shuai (2000)
PNAS 97, 5267-5272
   Abstract »    Full Text »    PDF »
Ischemia-induced STAT-1 Expression and Activation Play a Critical Role in Cardiomyocyte Apoptosis.
A. Stephanou, B. K. Brar, T. M. Scarabelli, A. K. Jonassen, D. M. Yellon, M. S. Marber, R. A. Knight, and D. S. Latchman (2000)
J. Biol. Chem. 275, 10002-10008
   Abstract »    Full Text »    PDF »
The IL-2 Receptor Promotes Lymphocyte Proliferation and Induction of the c-myc, bcl-2, and bcl-x Genes Through the trans-Activation Domain of Stat5.
J. D. Lord, B. C. McIntosh, P. D. Greenberg, and B. H. Nelson (2000)
J. Immunol. 164, 2533-2541
   Abstract »    Full Text »    PDF »
Thrombin Inhibits Tumor Cell Growth in Association with Up-regulation of p21waf/cip1 and Caspases via a p53-independent, STAT-1-dependent Pathway.
Y.-Q. Huang, J.-J. Li, and S. Karpatkin (2000)
J. Biol. Chem. 275, 6462-6468
   Abstract »    Full Text »    PDF »
Interferon-{gamma} Induces Interleukin-1 Converting Enzyme Expression in Pancreatic Islets by an Interferon Regulatory Factor-1-Dependent Mechanism.
A. E. Karlsen, D. Pavlovic, K. Nielsen, J. Jensen, H. U. Andersen, F. Pociot, T. Mandrup-Poulsen, D. L. Eizirik, and J. Nerup (2000)
J. Clin. Endocrinol. Metab. 85, 830-836
   Abstract »    Full Text »
STAT1 Affects Lymphocyte Survival and Proliferation Partially Independent of Its Role Downstream of IFN-{gamma}.
C.-K. Lee, E. Smith, R. Gimeno, R. Gertner, and D. E. Levy (2000)
J. Immunol. 164, 1286-1292
   Abstract »    Full Text »    PDF »
Activation of the Stat3 Signaling Pathway Is Required for Differentiation by Interleukin-6 in PC12-E2 Cells.
Y. Y. Wu and R. A. Bradshaw (2000)
J. Biol. Chem. 275, 2147-2156
   Abstract »    Full Text »    PDF »


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