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Inflammatory cardiac valvulitis in TAX1BP1-deficient mice through selective NF-kappaB activation.

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.

SUBMITTER: Iha H

PROVIDER: S-EPMC2262037 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

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Inflammatory cardiac valvulitis in TAX1BP1-deficient mice through selective NF-kappaB activation.

Iha Hidekatsu H Peloponese Jean-Marie JM Verstrepen Lynn L Zapart Grzegorz G Ikeda Fumiyo F Smith C Dahlem CD Starost Matthew F MF Yedavalli Venkat V Heyninck Karen K Dikic Ivan I Beyaert Rudi R Jeang Kuan-Teh KT

The EMBO journal 20080131 4

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 dev ...[more]

PMID: 18239685

Dataset Information

Inflammatory cardiac valvulitis in TAX1BP1-deficient mice through selective NF-kappaB activation.

Publications

Inflammatory cardiac valvulitis in TAX1BP1-deficient mice through selective NF-kappaB activation.

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