@article{e2acf613efa343fdb9e8c9dcdde91bda,
title = "Activation of the Iκb kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain",
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.",
author = "Li Deng and Chen Wang and Erika Spencer and Liyong Yang and Amy Braun and Jianxin You and Clive Slaughter and Cecile Pickart and Chen, {Zhijian J.}",
note = "Funding Information: We thank Dr. Jun Ichiro Inoue for TRAF6 cDNA, Dr. Allan Weissman for GST-Ubc13 and GST-Ubc5c cDNA, Dr. Carol Sibley for 70Z and 1.3E2 cells, Dr. Stephen Hobbs for pEF-IRES-P vector, Roseanne Hofmann for myc-K63 Ub protein, Carolyn Moomaw and Steve Afendis for peptide mass fingerprinting analysis, and Alisha Tizenor for graphic work. We are grateful to Drs. Tom Maniatis, Joseph Goldstein, Eric Olson, and Jin Jiang for critically reading the manuscript. This work was supported in part by the National Institutes of Health (GM 59203 to Z. J. C and GM 60372 to C. M. P), a grant from the Welch Foundation (Z. J. C), and by the American Heart Association-Texas Affiliates (Z. J. C). Z. J. C is a Searle Scholar supported by The Chicago Community Trust. ",
year = "2000",
month = oct,
day = "13",
doi = "10.1016/S0092-8674(00)00126-4",
language = "English (US)",
volume = "103",
pages = "351--361",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",
}