Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain.
Journal - Cell (UNITED STATES )
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.
|ISSN : ||0092-8674|
|Mesh Heading : ||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 Ubiquitin-Conjugating Enzymes Ubiquitin-Protein Ligases Ubiquitins isolation & purification|
|Mesh Heading Relevant : ||Transcription Factors metabolism metabolism metabolism metabolism metabolism|