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Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain.

Cell | Oct 13, 2000

http://www.ncbi.nlm.nih.gov/pubmed/11057907

TRAF6 is a signal transducer in the NF-kappaB pathway that activates IkappaB kinase (IKK) in response to proinflammatory cytokines. We have purified a heterodimeric protein complex that links TRAF6 to IKK activation. Peptide mass fingerprinting analysis reveals that this complex is composed of the ubiquitin conjugating enzyme Ubc13 and the Ubc-like protein Uev1A. We find that TRAF6, a RING domain protein, functions together with Ubc13/Uev1A to catalyze the synthesis of unique polyubiquitin chains linked through lysine-63 (K63) of ubiquitin. Blockade of this polyubiquitin chain synthesis, but not inhibition of the proteasome, prevents the activation of IKK by TRAF6. These results unveil a new regulatory function for ubiquitin, in which IKK is activated through the assembly of K63-linked polyubiquitin chains.

Pubmed ID: 11057907 RIS Download

Mesh terms: Amino Acid Sequence | Biopolymers | Cell-Free System | Cloning, Molecular | Dimerization | Enzyme Activation | HeLa Cells | Humans | I-kappa B Kinase | Ligases | Molecular Sequence Data | Peptide Mapping | Polyubiquitin | Protein-Serine-Threonine Kinases | Proteins | Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization | TNF Receptor-Associated Factor 6 | Transcription Factors | Ubiquitin-Conjugating Enzymes | Ubiquitin-Protein Ligases | Ubiquitins

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Associated grants

  • Agency: NIGMS NIH HHS, Id: GM 59203
  • Agency: NIGMS NIH HHS, Id: GM 60372

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