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TAK1-binding protein 2 facilitates ubiquitination of TRAF6 and assembly of TRAF6 with IKK in the IL-1 signaling pathway.

TAK1 mitogen-activated protein kinase kinase kinase participates in the Interleukin-1 (IL-1) signaling pathway by mediating activation of JNK, p38, and NF-kappaB. TAK1-binding protein 2 (TAB2) was previously identified as an adaptor that links TAK1 to an upstream signaling intermediate, tumor necrosis factor receptor-associated factor 6 (TRAF6). Recently, ubiquitination of TRAF6 was shown to play an essential role in the activation of TAK1. However, the mechanism by which IL-1 induces TRAF6 ubiquitination remains to be elucidated. Here we report that TAB2 functions to facilitate TRAF6 ubiquitination and thereby mediates IL-1-induced cellular events. A conserved ubiquitin binding domain in TAB2, the CUE domain, is important for this function. We also found that TAB2 promotes the assembly of TRAF6 with a downstream kinase, IkappaB kinase (IKK). These results show that TAB2 acts as a multifunctional signaling molecule, facilitating both IL-1-dependent TRAF6 ubiquitination and assembly of the IL-1 signaling complex.

Pubmed ID: 15836773

Authors

  • Kishida S
  • Sanjo H
  • Akira S
  • Matsumoto K
  • Ninomiya-Tsuji J

Journal

Genes to cells : devoted to molecular & cellular mechanisms

Publication Data

May 19, 2005

Associated Grants

  • Agency: NIAMS NIH HHS, Id: AR050972
  • Agency: NIGMS NIH HHS, Id: GM068812
  • Agency: NIGMS NIH HHS, Id: R01 GM068812
  • Agency: NIAMS NIH HHS, Id: R21 AR050972

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • I-kappa B Kinase
  • Interleukin-1
  • Mice
  • Mutation
  • NF-kappa B
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases
  • Signal Transduction
  • TNF Receptor-Associated Factor 6
  • Ubiquitin