The human T-cell leukemia virus type 1 tax oncoprotein requires the ubiquitin-conjugating enzyme Ubc13 for NF-κB activation
The human T-cell leukemia virus type 1 tax oncoprotein requires the ubiquitin-conjugating enzyme Ubc13 for NF-κB activation
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DOI：
10.1128/jvi.01790-07
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发表时间：
2007-12-01
影响因子：
5.4
通讯作者：
Harhaj, Edward W.
中科院分区：
文献类型：
--
作者：
Shembade, Noula;Harhaj, Nicole S.;Harhaj, Edward W.
人T细胞白血病病毒1 Tax癌蛋白的泛素化提供了促进Tax介导的NF-κ B活化的重要调节机制。然而，类型的多聚泛素链连接和所需的税收泛素化的主机因素尚未确定。在这里，我们证明，税收聚泛素链主要由赖氨酸63连接的链。此外，Tax的泛素化主要依赖于E2泛素结合酶Ubc 13。Tax与Ubc 13相互作用，小干扰RNA介导的Ubc 13表达的敲低消除了Tax泛素化和NF-κ B的活化。缺乏Ubc 13的小鼠成纤维细胞表现出NF-κ B的Tax活化受损，尽管正常的肿瘤坏死因子和白细胞介素-1介导的NF-κ B活化。最后，在没有Tax泛素化和Ubc 13表达的情况下，Tax与NEMO的相互作用被破坏，这表明Tax泛素化对NEMO结合至关重要。总的来说，我们的研究结果表明，Ubc 13是必不可少的税收泛素化，其与NEMO的相互作用，和税收介导的NF-κ B激活。
Ubiquitination of the human T-cell leukemia virus 1 Tax oncoprotein provides an important regulatory mechanism that promotes the Tax-mediated activation of NF-kappa B. However, the type of polyubiquitin chain linkages and the host factors that are required for Tax ubiquitination have not been identified. Here, we demonstrate that Tax polyubiquitin chains are composed predominantly of lysine 63-linked chains. Furthermore, the ubiquitination of Tax is critically dependent on the E2 ubiquitin-conjugating enzyme Ubc13. Tax interacts with Ubc13, and small interfering RNA-mediated knockdown of Ubc13 expression abrogates Tax ubiquitination and the activation of NF-kappa B. Mouse fibroblasts lacking Ubc13 exhibit impaired Tax activation of NF-kappa B despite normal tumor necrosis factor- and interleukin-l-mediated NF-kappa B activation. Finally, the interaction of Tax with NEMO is disrupted in the absence of Tax ubiquitination and Ubc13 expression, suggesting that Tax ubiquitination is critical for NEMO binding. Collectively, our results reveal that Ubc13 is essential for Tax ubiquitination, its interaction with NEMO, and Tax-mediated NF-kappa B activation.