[HTML][HTML] Activation of the IκB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain

L Deng, C Wang, E Spencer, L Yang, A Braun, J You… - Cell, 2000 - cell.com
L Deng, C Wang, E Spencer, L Yang, A Braun, J You, C Slaughter, C Pickart, ZJ Chen
Cell, 2000cell.com
TRAF6 is a signal transducer in the NF-κB pathway that activates IκB 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 …
Abstract
TRAF6 is a signal transducer in the NF-κB pathway that activates IκB 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.
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