Lipopolysaccharide-mediated Interferon Regulatory Factor Activation Involves TBK1-IKKϵ-dependent Lys63-linked Polyubiquitination and Phosphorylation of TANK/I-TRAF
| Autor: | Eric Muraille, Pierre Close, Jean-Paul Chapelle, Alain Chariot, Jacques Piette, Keith Brown, Emmanuel Dejardin, Felicia Alina Patrascu, Tieu-Lan Chau, Romain Gioia, Jean-Stéphane Gatot, Michael Warnier, Ulrich Siebenlist |
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| Rok vydání: | 2007 |
| Předmět: |
Lipopolysaccharides
Scaffold protein macromolecular substances Protein Serine-Threonine Kinases Kidney Transfection environment and public health Biochemistry Cell Line Mice TANK-binding kinase 1 Genes Reporter Two-Hybrid System Techniques Animals Humans Phosphorylation RNA Small Interfering Kinase activity Luciferases Molecular Biology Adaptor Proteins Signal Transducing biology Kinase Lysine Macrophages Ubiquitination Cell Biology I-kappa B Kinase Ubiquitin ligase Cell biology Enzyme Activation Interferon Regulatory Factors biology.protein RNA Interference Signal transduction IRF3 HeLa Cells |
| Zdroj: | Journal of Biological Chemistry. 282:31131-31146 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m701690200 |
| Popis: | Type I interferon gene induction relies on IKK-related kinase TBK1 and IKKepsilon-mediated phosphorylations of IRF3/7 through the Toll-like receptor-dependent signaling pathways. The scaffold proteins that assemble these kinase complexes are poorly characterized. We show here that TANK/ITRAF is required for the TBK1- and IKKepsilon-mediated IRF3/7 phosphorylations through some Toll-like receptor-dependent pathways and is part of a TRAF3-containing complex. Moreover, TANK is dispensable for the early phase of double-stranded RNA-mediated IRF3 phosphorylation. Interestingly, TANK is heavily phosphorylated by TBK1-IKKepsilon upon lipopolysaccharide stimulation and is also subject to lipopolysaccharide- and TBK1-IKKepsilon-mediated Lys(63)-linked polyubiquitination, a mechanism that does not require TBK1-IKKepsilon kinase activity. Thus, we have identified TANK as a scaffold protein that assembles some but not all IRF3/7-phosphorylating TBK1-IKKepsilon complexes and demonstrated that these kinases possess two functions, namely the phosphorylation of both IRF3/7 and TANK as well as the recruitment of an E3 ligase for Lys(63)-linked polyubiquitination of their scaffold protein, TANK. |
| Databáze: | OpenAIRE |
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