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

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

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

Nuclear factor kappa B (NF-κB) is a key mediator of inflammation. Unchecked NF-κB signalling can engender autoimmune pathologies and cancers. Here, we show that Tax1-binding protein 1 (TAX1BP1) is a negative regulator of TNF-α- and IL-1β-induced NF-κB activation and that binding to mono- and polyubiquitin by a ubiquitin-binding Zn finger domain in TAX1BP1 is needed for TRAF6 association and NF-κB 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-α and IL-1β. TAX1BP1-/- cells are more highly activated for NF-κB than control cells when stimulated with TNF-α or IL-1β. Mechanistically, TAX1BP1 acts in NF-κB signalling as an essential adaptor between A20 and its targets.

Original languageEnglish
Pages (from-to)629-641
Number of pages13
JournalEMBO Journal
Volume27
Issue number4
DOIs
Publication statusPublished - Feb 20 2008

Fingerprint

NF-kappa B
Carrier Proteins
Chemical activation
Interleukin-1
TNF Receptor-Associated Factor 6
Polyubiquitin
Inflammation Mediators
Pathology
Ubiquitin
mouse TAX1BP1 protein
Association reactions
Neoplasms

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Iha, H., Peloponese, J. M., Verstrepen, L., Zapart, G., Ikeda, F., Smith, C. D., ... Jeang, K. T. (2008). Inflammatory cardiac valvulitis in TAX1BP1-deficient mice through selective NF-κB activation. EMBO Journal, 27(4), 629-641. https://doi.org/10.1038/emboj.2008.5

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

In: EMBO Journal, Vol. 27, No. 4, 20.02.2008, p. 629-641.

Research output: Contribution to journalArticle

Iha, H, Peloponese, JM, Verstrepen, L, Zapart, G, Ikeda, F, Smith, CD, Starost, MF, Yedavalli, V, Heyninck, K, Dikic, I, Beyaert, R & Jeang, KT 2008, 'Inflammatory cardiac valvulitis in TAX1BP1-deficient mice through selective NF-κB activation', EMBO Journal, vol. 27, no. 4, pp. 629-641. https://doi.org/10.1038/emboj.2008.5
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. / Inflammatory cardiac valvulitis in TAX1BP1-deficient mice through selective NF-κB activation. In: EMBO Journal. 2008 ; Vol. 27, No. 4. pp. 629-641.
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