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

doi:10.1016/S0092-8674(00)00126-4

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Activation of the IκB Kinase Complex by TRAF6 Requires a Dimeric Ubiquitin-Conjugating Enzyme Complex and a Unique Polyubiquitin Chain

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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 and Zhijian J Chen

Cell (Cambridge), Vol.103(2), pp.351-361

10/13/2000

DOI: https://doi.org/10.1016/S0092-8674(00)00126-4

PMID: 11057907

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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Title: Activation of the IκB Kinase Complex by TRAF6 Requires a Dimeric Ubiquitin-Conjugating Enzyme Complex and a Unique Polyubiquitin Chain
Creators: Li Deng - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas , Texas 75390, USA
Chen Wang - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas , Texas 75390, USA
Erika Spencer - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas , Texas 75390, USA
Liyong Yang - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas , Texas 75390, USA
Amy Braun - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas , Texas 75390, USA
Jianxin You - Department of Biochemistry, School of Public Health, Johns Hopkins University, Baltimore , Maryland 21205, USA
Clive Slaughter - Department of Biochemistry and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas , Texas 75390, USA
Cecile Pickart - Department of Biochemistry, School of Public Health, Johns Hopkins University, Baltimore , Maryland 21205, USA
Zhijian J Chen - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas , Texas 75390, USA
Publication Details: Cell (Cambridge), Vol.103(2), pp.351-361
Publisher: Elsevier Inc
Identifiers: 9923973193901921
Academic Unit: Department of Chemistry
Language: English
Resource Type: Journal article

Activation of the IκB Kinase Complex by TRAF6 Requires a Dimeric Ubiquitin-Conjugating Enzyme Complex and a Unique Polyubiquitin Chain

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