Activation of the IκB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain
Activation of the IκB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain
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DOI：
10.1016/s0092-8674(00)00126-4
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发表时间：
2000-10-13
期刊：
影响因子：
64.5
通讯作者：
Chen, ZJ
中科院分区：
文献类型：
--
作者：
Deng, L;Wang, C;Chen, ZJ
TRAF6是NF-KAPPA B途径中的信号传感器，该途径激活I Kappa B激酶（IKK），以响应促炎细胞因子。我们已经纯化了将TRAF6与IKK激活联系起来的异二聚体蛋白复合物。肽质量指纹分析表明，该复合物由泛素结合酶UBC13和UBC样蛋白UEV1A组成。我们发现Traf6（一种环域蛋白质）与UBC13/UEV1A一起起作用，以催化通过泛素赖氨酸-63（K63）连接的独特多泛素链的合成。这种多泛素链合成的封锁，但没有抑制蛋白酶体，可以防止Traf6的IKK激活。这些结果揭示了泛素的新调节功能，其中IKK通过组装K63连接的多泛素链被激活。
TRAF6 is a signal transducer in the NF-kappa B pathway that activates I kappa B 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.