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- Title
Inflammatory cardiac valvulitis in TAX1BP1-deficient mice through selective NF-kappaB activation.
- Authors
Iha, Hidekatsu; Peloponese, Jean-Marie; Verstrepen, Lynn; Zapart, Grzegorz; Ikeda, Fumiyo; Smith, C Dahlem; Starost, Matthew F; Yedavalli, Venkat; Heyninck, Karen; Dikic, Ivan; Beyaert, Rudi; Jeang, Kuan-Teh
- Abstract
Nuclear factor kappa B (NF-kappaB) is a key mediator of inflammation. Unchecked NF-kappaB signalling can engender autoimmune pathologies and cancers. Here, we show that Tax1-binding protein 1 (TAX1BP1) is a negative regulator of TNF-alpha- and IL-1beta-induced NF-kappaB activation and that binding to mono- and polyubiquitin by a ubiquitin-binding Zn finger domain in TAX1BP1 is needed for TRAF6 association and NF-kappaB 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-alpha and IL-1beta. TAX1BP1-/- cells are more highly activated for NF-kappaB than control cells when stimulated with TNF-alpha or IL-1beta. Mechanistically, TAX1BP1 acts in NF-kappaB signalling as an essential adaptor between A20 and its targets.
- Publication
The EMBO journal, 2008, Vol 27, Issue 4, p629
- ISSN
1460-2075
- Publication type
Journal Article
- DOI
10.1038/emboj.2008.5