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

A20 is a cytoplasmic zinc finger protein that inhibits nuclear factor B (NF-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-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-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.

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

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TRAF6 and A20 Regulate Lysine 63-Linked Ubiquitination of Beclin-1 to Control TLR4-Induced Autophagy.

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BCR ligation induced by IgM stimulation results in gene expression and functional changes only in IgVH unmutated chronic lymphocytic leukemia (CLL) cells.

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Blood 112, 782-792
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Structural Basis for Ubiquitin Recognition by the Otu1 Ovarian Tumor Domain Protein.

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A20 is a negative regulator of BCL10- and CARMA3-mediated activation of NF-{kappa}B.

R. Stilo, E. Varricchio, D. Liguoro, A. Leonardi, and P. Vito (2008)
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Recent advances in the genetics of RA susceptibility.

J. Bowes and A. Barton (2008)
Rheumatology 47, 399-402
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NF-{kappa}B Suppression by the Deubiquitinating Enzyme Cezanne: A NOVEL NEGATIVE FEEDBACK LOOP IN PRO-INFLAMMATORY SIGNALING.

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J. Biol. Chem. 283, 7036-7045
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Homeostatic MyD88-dependent signals cause lethal inflamMation in the absence of A20.

E. E. Turer, R. M. Tavares, E. Mortier, O. Hitotsumatsu, R. Advincula, B. Lee, N. Shifrin, B. A. Malynn, and A. Ma (2008)
J. Exp. Med. 205, 451-464
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PNAS 105, 1279-1284
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The protective effect of A20 on atherosclerosis in apolipoprotein E-deficient mice is associated with reduced expression of NF-{kappa}B target genes.

S. Wolfrum, D. Teupser, M. Tan, K. Y. Chen, and J. L. Breslow (2007)
PNAS 104, 18601-18606
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I{kappa}B Kinase {beta} Phosphorylates the K63 Deubiquitinase A20 To Cause Feedback Inhibition of the NF-{kappa}B Pathway.

J. E. Hutti, B. E. Turk, J. M. Asara, A. Ma, L. C. Cantley, and D. W. Abbott (2007)
Mol. Cell. Biol. 27, 7451-7461
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FAF1 Suppresses I{kappa}B Kinase (IKK) Activation by Disrupting the IKK Complex Assembly.

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J. Biol. Chem. 282, 27572-27577
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Coordinated Regulation of Toll-Like Receptor and NOD2 Signaling by K63-Linked Polyubiquitin Chains.

D. W. Abbott, Y. Yang, J. E. Hutti, S. Madhavarapu, M. A. Kelliher, and L. C. Cantley (2007)
Mol. Cell. Biol. 27, 6012-6025
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Beyond I{kappa}Bs: alternative regulation of NF-{kappa}B activity.

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A Drosophila ortholog of the human cylindromatosis tumor suppressor gene regulates triglyceride content and antibacterial defense.

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ABIN-3: a Molecular Basis for Species Divergence in Interleukin-10-Induced Anti-Inflammatory Actions.

B. K. Weaver, E. Bohn, B. A. Judd, M. P. Gil, and R. D. Schreiber (2007)
Mol. Cell. Biol. 27, 4603-4616
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Deubiquitinating enzyme CYLD negatively regulates the ubiquitin-dependent kinase Tak1 and prevents abnormal T cell responses.

W. W. Reiley, W. Jin, A. J. Lee, A. Wright, X. Wu, E. F. Tewalt, T. O. Leonard, C. C. Norbury, L. Fitzpatrick, M. Zhang, et al. (2007)
J. Exp. Med. 204, 1475-1485
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TLRs in the Gut.IV. Negative regulation of Toll-like receptors and intestinal homeostasis: addition by subtraction.

O. Shibolet and D. K. Podolsky (2007)
Am J Physiol Gastrointest Liver Physiol 292, G1469-G1473
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Hepatic Tumor Necrosis Factor Signaling and Nuclear Factor-{kappa}B: Effects on Liver Homeostasis and Beyond.

A. Wullaert, G. van Loo, K. Heyninck, and R. Beyaert (2007)
Endocr. Rev. 28, 365-386
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Transcriptional Signature of Epidermal Keratinocytes Subjected to in Vitro Scratch Wounding Reveals Selective Roles for ERK1/2, p38, and Phosphatidylinositol 3-Kinase Signaling Pathways.

G. Fitsialos, A.-A. Chassot, L. Turchi, M. A. Dayem, K. LeBrigand, C. Moreilhon, G. Meneguzzi, R. Busca, B. Mari, P. Barbry, et al. (2007)
J. Biol. Chem. 282, 15090-15102
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Gnotobiotic IL-10-/-;NF-{kappa}BEGFP Mice Reveal the Critical Role of TLR/NF-{kappa}B Signaling in Commensal Bacteria-Induced Colitis.

T. Karrasch, J.-S. Kim, M. Muhlbauer, S. T. Magness, and C. Jobin (2007)
J. Immunol. 178, 6522-6532
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Elevated amount of Toll-like receptor 4 mRNA in bronchial epithelial cells is associated with airway inflammation in horses with recurrent airway obstruction.

A. Berndt, F. J. Derksen, P. J. Venta, S. Ewart, V. Yuzbasiyan-Gurkan, and N. E. Robinson (2007)
Am J Physiol Lung Cell Mol Physiol 292, L936-L943
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CD44 Is a Negative Regulator of Acute Pulmonary Inflammation and Lipopolysaccharide-TLR Signaling in Mouse Macrophages.

J. Liang, D. Jiang, J. Griffith, S. Yu, J. Fan, X. Zhao, R. Bucala, and P. W. Noble (2007)
J. Immunol. 178, 2469-2475
 |  Abstract »  |  Full Text »  |  PDF »