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Science 289 (5488): 2350-2354

Copyright © 2000 by the American Association for the Advancement of Science

Failure to Regulate TNF-Induced NF-kappa B and Cell Death Responses in A20-Deficient Mice

Eric G. Lee,* David L. Boone,* Sophia Chai, Shon L. Libby, Marcia Chien, James P. Lodolce, Averil Madagger

A20 is a cytoplasmic zinc finger protein that inhibits nuclear factor kappa B (NF-kappa B) activity and tumor necrosis factor (TNF)-mediated programmed cell death (PCD). TNF dramatically increases A20 messenger RNA expression in all tissues. Mice deficient for A20 develop severe inflammation and cachexia, are hypersensitive to both lipopolysaccharide and TNF, and die prematurely. A20-deficient cells fail to terminate TNF-induced NF-kappa B responses. These cells are also more susceptible than control cells to undergo TNF-mediated PCD. Thus, A20 is critical for limiting inflammation by terminating TNF-induced NF-kappa B responses in vivo.

Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, MC 6084, Chicago, IL 60637, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: ama{at}medicine.bsd.uchicago.edu

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X. Sun, J. Yin, M. A. Starovasnik, W. J. Fairbrother, and V. M. Dixit (2002)
J. Biol. Chem. 277, 9505-9511
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Deficiency of c-Jun-NH2-terminal Kinase-1 in Mice Enhances Skin Tumor Development by 12-O-Tetradecanoylphorbol-13-Acetate.
Q.-B. She, N. Chen, A. M. Bode, R. A. Flavell, and Z. Dong (2002)
Cancer Res. 62, 1343-1348
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Molecular Regulation of Urothelial Renewal and Host Defenses during Infection with Uropathogenic Escherichia coli.
I. U. Mysorekar, M. A. Mulvey, S. J. Hultgren, and J. I. Gordon (2002)
J. Biol. Chem. 277, 7412-7419
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All TRAFs are not created equal: common and distinct molecular mechanisms of TRAF-mediated signal transduction.
J. Y. Chung, Y. C. Park, H. Ye, and H. Wu (2002)
J. Cell Sci. 115, 679-688
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Role of NF-{kappa}B in Endotoxemia-Induced Alterations of Lung Neutrophil Apoptosis.
J. G. Kupfner, J. J. Arcaroli, H.-K. Yum, S. G. Nadler, K.-Y. Yang, and E. Abraham (2001)
J. Immunol. 167, 7044-7051
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Oxidized Low Density Lipoprotein Exposure Alters the Transcriptional Response of Macrophages to Inflammatory Stimulus.
T. Mikita, G. Porter, R. M. Lawn, and D. Shiffman (2001)
J. Biol. Chem. 276, 45729-45739
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