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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Beyaert, R. Heyninck, K. Fiers, W. De Valck, D. Vanden Berghe, W. Van Criekinge, W. Contreras, R. Haegeman, G. |
| Description | Author Affiliation: Heyninck K ( Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology, University of Ghent, B-9000 Ghent, Belgium.) |
| Abstract | The zinc finger protein A20 is a tumor necrosis factor (TNF)– and interleukin 1 (IL-1)-inducible protein that negatively regulates nuclear factor-kappa B (NF-κB)–dependent gene expression. However, the molecular mechanism by which A20 exerts this effect is still unclear. We show that A20 does not inhibit TNF- induced nuclear translocation and DNA binding of NF-κB, although it completely prevents the TNF- induced activation of an NF-κB–dependent reporter gene, as well as TNF-induced IL-6 and granulocyte macrophage–colony stimulating factor gene expression. Moreover, NF-κB activation induced by overexpression of the TNF receptor–associated proteins TNF receptor–associated death domain protein (TRADD), receptor interacting protein (RIP), and TNF recep- tor–associated factor 2 (TRAF2) was also inhibited by expression of A20, whereas NF-κB activation induced by overexpression of NF-κB–inducing kinase (NIK) or the human T cell leukemia virus type 1 (HTLV-1) Tax was unaffected. These results demonstrate that A20 inhibits NF-κB–dependent gene expression by interfering with a novel TNF-induced and RIP- or TRAF2-mediated pathway that is different from the NIK–IκB kinase pathway and that is specifically involved in the transactivation of NF-κB. Via yeast two-hybrid screening, we found that A20 binds to a novel protein, ABIN, which mimics the NF-κB inhibiting effects of A20 upon overexpression, suggesting that the effect of A20 is mediated by its interaction with this NF-κB inhibiting protein, ABIN. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 7 |
| Volume Number | 145 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 1999-06-28 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Carrier Proteins Metabolism Mitogen-Activated Protein Kinases NF-kappa B Proteins Transcriptional Activation Tumor Necrosis Factor Receptor-Associated Peptides And Proteins Tumor Necrosis Factor-alpha Antagonists & Inhibitors Animals Calcium-Calmodulin-Dependent Protein Kinases Genetics Cell Line Cell Nucleus Drug Effects Cysteine Endopeptidases DNA DNA-Binding Proteins Enzyme Activation Gene Products, Tax Granulocyte-Macrophage Colony-Stimulating Factor Interleukin-6 Intracellular Signaling Peptides And Proteins Mice Molecular Sequence Data Nuclear Proteins Physiology Protein Binding Protein-Serine-Threonine Kinases Chemistry Receptor-Interacting Protein Serine-Threonine Kinases Signal Transduction TNF Receptor-Associated Death Domain Protein TNF Receptor-Associated Factor 1 TNF Receptor-Associated Factor 2 Trans-Activators Pharmacology Yeasts Zinc Fingers P38 Mitogen-Activated Protein Kinases Research Support, Non-U.S. Gov't Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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