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| Subject Categories: Signal Transduction |
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| The EMBO Journal
(2008) 27, 629–641, doi:10.1038/emboj.2008.5 Published online 31 January 2008 |
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Inflammatory cardiac valvulitis in TAX1BP1-deficient mice through selective NF- B activation |
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| Hidekatsu Iha1, 6, 7, Jean-Marie Peloponese1, 7, Lynn Verstrepen2, Grzegorz Zapart3, Fumiyo Ikeda3, C Dahlem Smith4, Matthew F Starost5, Venkat Yedavalli1, Karen Heyninck2, Ivan Dikic3, Rudi Beyaert2 and Kuan-Teh Jeang1 |
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1 Laboratory of Molecular Microbiology, Molecular Virology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA 2 Department for Molecular Biomedical Research, Unit of Molecular Signal Transduction in Inflammation, Ghent University—VIB, Ghent (Zwijnaarde), Belgium 3 Institute for Biochemistry II, Goethe University Medical School, Frankfurt, Germany 4 Pathology/Histotechnology Laboratory, SAIC-Frederick Inc., NCI-FCR, Frederick, MD, USA 5 Division of Veterinary Resources, National Institutes of Health, Bethesda, MD, USA 6 Department of Infectious Diseases, Faculty of Medicine, Oita University Idaiga-oka, Hasama Yufu, Japan To whom correspondence should be addressed Kuan-Teh Jeang, Laboratory of Molecular Microbiology, Molecular Virology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 4, Room 306, 9000 Rockville Pike, Bethesda, MD 20892-0460, USA. Tel.: +1 301 496 6680; Fax: +1 301 480 3686; E-mail: kjeang@niaid.nih.gov 7 These authors contributed equally to this work Received 18 September 2007; Accepted 4 January 2008; Published online 31 January 2008. |
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| Abstract |
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Nuclear factor kappa B (NF-B) is a key mediator of inflammation. Unchecked NF-B signalling can engender autoimmune pathologies and cancers. Here, we show that Tax1-binding protein 1 (TAX1BP1) is a negative regulator of TNF- - and IL-1 -induced NF-B activation and that binding to mono- and polyubiquitin by a ubiquitin-binding Zn finger domain in TAX1BP1 is needed for TRAF6 association and NF-B inhibition. Mice genetically knocked out for TAX1BP1 are born normal, but develop age-dependent inflammatory cardiac valvulitis, die prematurely, and are hypersensitive to low doses of TNF- and IL-1. TAX1BP1-/- cells are more highly activated for NF-B than control cells when stimulated with TNF- or IL-1. Mechanistically, TAX1BP1 acts in NF-B signalling as an essential adaptor between A20 and its targets. |
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| Keywords: A20, NF-B, Tax, TAX1BP1, TRAF6 |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSNature Immunology News and Views (01 Mar 2008) Smads keep TABs on inflammation Nature Immunology News and Views (01 May 2007) RESEARCHInflammatory cardiac valvulitis in TAX1BP1-deficient mice through selective NF-κB activation The EMBO Journal Article Inflammatory cardiac valvulitis in TAX1BP1-deficient mice through selective NF-κB activation The EMBO Journal Article (20 Feb 2008) |
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