• Register
Forgot Password

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


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


Association of the adaptor TANK with the I kappa B kinase (IKK) regulator NEMO connects IKK complexes with IKK epsilon and TBK1 kinases.

Canonical activation of NF-kappa B is mediated via phosphorylation of the inhibitory I kappa B proteins by the I kappa B kinase complex (IKK). IKK is composed of a heterodimer of the catalytic IKK alpha and IKK beta subunits and a presumed regulatory protein termed NEMO (NF-kappa B essential modulator) or IKK gamma. NEMO/IKK gamma is indispensable for activation of the IKKs in response to many signals, but its mechanism of action remains unclear. Here we identify TANK (TRAF family member-associated NF-kappa B activator) as a NEMO/IKK gamma-interacting protein via yeast two-hybrid analyses. This interaction is confirmed in mammalian cells, and the domains required are mapped. TANK was previously shown to assist NF-kappa B activation in a complex with TANK-binding kinase 1 (TBK1) or IKK epsilon, two kinases distantly related to IKK alpha/beta, but the underlying mechanisms remained unknown. Here we show that TBK1 and IKK epsilon synergize with TANK to promote interaction with the IKKs. The TANK binding domain within NEMO/IKK gamma is required for proper functioning of this IKK subunit. These results indicate that TANK can synergize with IKK epsilon or TBK1 to link them to IKK complexes, where the two kinases may modulate aspects of NF-kappa B activation.

Pubmed ID: 12133833


  • Chariot A
  • Leonardi A
  • Muller J
  • Bonif M
  • Brown K
  • Siebenlist U


The Journal of biological chemistry

Publication Data

October 4, 2002

Associated Grants


Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Cloning, Molecular
  • Dimerization
  • HeLa Cells
  • Humans
  • I-kappa B Kinase
  • Kidney
  • Liver
  • Mitogen-Activated Protein Kinases
  • NF-kappa B
  • Protein Binding
  • Protein Biosynthesis
  • Protein Subunits
  • Protein-Serine-Threonine Kinases
  • Proteins
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae
  • Transfection