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

Li Deng, Chen Wang, Erika Spencer, Liyong Yang, Amy Braun, Jianxin You, Clive Slaughter, Cecile Pickart, Zhijian J. Chen

Research output: Contribution to journalArticle

1297 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)351-361
Number of pages11
JournalCell
Volume103
Issue number2
StatePublished - Oct 13 2000

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TNF Receptor-Associated Factor 6
Polyubiquitin
Ubiquitin-Conjugating Enzymes
Phosphotransferases
Chemical activation
Ubiquitin
Proteins
Peptide Mapping
Proteasome Endopeptidase Complex
Transducers
Lysine
Cytokines
Peptides

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Activation of the Iκb kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. / Deng, Li; Wang, Chen; Spencer, Erika; Yang, Liyong; Braun, Amy; You, Jianxin; Slaughter, Clive; Pickart, Cecile; Chen, Zhijian J.

In: Cell, Vol. 103, No. 2, 13.10.2000, p. 351-361.

Research output: Contribution to journalArticle

Deng, L, Wang, C, Spencer, E, Yang, L, Braun, A, You, J, Slaughter, C, Pickart, C & Chen, ZJ 2000, 'Activation of the Iκb kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain', Cell, vol. 103, no. 2, pp. 351-361.
Deng, Li ; Wang, Chen ; Spencer, Erika ; Yang, Liyong ; Braun, Amy ; You, Jianxin ; Slaughter, Clive ; Pickart, Cecile ; Chen, Zhijian J. / Activation of the Iκb kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. In: Cell. 2000 ; Vol. 103, No. 2. pp. 351-361.
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