Hidekatsu Iha, Jean-Marie Peloponese, Lynn Verstrepen, Grzegorz Zapart, Fumiyo Ikeda, C Dahlem Smith, Matthew F Starost, Venkat Yedavalli, Karen Heyninck, Ivan Dikic, Rudi Beyaert, Kuan-Teh Jeang
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...
February 20, 2008: EMBO Journal