Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

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

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.

Pubmed ID: 18239685


  • Iha H
  • Peloponese JM
  • Verstrepen L
  • Zapart G
  • Ikeda F
  • Smith CD
  • Starost MF
  • Yedavalli V
  • Heyninck K
  • Dikic I
  • Beyaert R
  • Jeang KT


The EMBO journal

Publication Data

February 20, 2008

Associated Grants

  • Agency: NCI NIH HHS, Id: N01-CO-12400
  • Agency: Intramural NIH HHS, Id:

Mesh Terms

  • Animals
  • Cysteine Endopeptidases
  • Female
  • GTPase-Activating Proteins
  • Heart Diseases
  • Heart Valves
  • Hypersensitivity
  • Inflammation
  • Interleukin-1beta
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B
  • Neoplasm Proteins
  • TNF Receptor-Associated Factor 6
  • Tumor Necrosis Factor-alpha