TRAF6对IkappaB激酶复合体的激活需要一个二聚体泛素缀合酶复合体和一条独特的多聚泛素链。

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

作者信息

Deng L, Wang C, Spencer E, Yang L, Braun A, You J, Slaughter C, Pickart C, Chen Z J

机构信息

Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas 75390, USA.

出版信息

Cell. 2000 Oct 13;103(2):351-61. doi: 10.1016/s0092-8674(00)00126-4.

DOI:10.1016/s0092-8674(00)00126-4

PMID:11057907

Abstract

TRAF6 is a signal transducer in the NF-kappaB pathway that activates IkappaB 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.

摘要

TRAF6是核因子κB（NF-κB）信号通路中的一种信号转导分子，可响应促炎细胞因子激活IκB激酶（IKK）。我们纯化了一种将TRAF6与IKK激活相联系的异源二聚体蛋白复合物。肽质量指纹图谱分析显示，该复合物由泛素缀合酶Ubc13和类Ubc蛋白Uev1A组成。我们发现，具有RING结构域的蛋白TRAF6与Ubc13/Uev1A共同作用，催化通过泛素赖氨酸-63（K63）连接的独特多聚泛素链的合成。阻断这种多聚泛素链的合成，而非抑制蛋白酶体，可阻止TRAF6激活IKK。这些结果揭示了泛素的一种新调节功能，即通过组装K63连接的多聚泛素链激活IKK。