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 language | English (US) |
|---|---|
| Pages (from-to) | 351-361 |
| Number of pages | 11 |
| Journal | Cell |
| Volume | 103 |
| Issue number | 2 |
| DOIs | |
| State | Published - Oct 13 2000 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
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 journal › Article
}
TY - JOUR
T1 - Activation of the Iκb kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain
AU - Deng, Li
AU - Wang, Chen
AU - Spencer, Erika
AU - Yang, Liyong
AU - Braun, Amy
AU - You, Jianxin
AU - Slaughter, Clive
AU - Pickart, Cecile
AU - Chen, Zhijian J.
PY - 2000/10/13
Y1 - 2000/10/13
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0034644474&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034644474&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(00)00126-4
DO - 10.1016/S0092-8674(00)00126-4
M3 - Article
C2 - 11057907
AN - SCOPUS:0034644474
VL - 103
SP - 351
EP - 361
JO - Cell
JF - Cell
SN - 0092-8674
IS - 2
ER -