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

Genes Cells. 2005 May;10(5):447-54. doi: 10.1111/j.1365-2443.2005.00852.x.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

  • Adaptor Proteins, Signal Transducing
  • Interleukin-1
  • NF-kappa B
  • TNF Receptor-Associated Factor 6
  • Tab2 protein, mouse
  • Ubiquitin
  • Protein-Serine-Threonine Kinases
  • Chuk protein, mouse
  • I-kappa B Kinase
  • Ikbkb protein, mouse
  • Ikbke protein, mouse