Ectromelia virus encodes a family of Ankyrin/F-box proteins that regulate NFκB
Ectromelia virus encodes a family of Ankyrin/F-box proteins that regulate NFκB
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DOI：
10.1016/j.virol.2014.08.030
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发表时间：
2014-11-01
期刊：
影响因子：
3.7
通讯作者：
Barry, Michele
中科院分区：
文献类型：
--
作者：
Buries, Kristin;van Buuren, Nicholas;Barry, Michele
痘病毒的一个显著特征是其抑制抗病毒应答的能力，包括核因子κ B（NF κ B）途径。NF κ B是一种转录因子，在细胞刺激前被隔离在细胞质中，并依赖SCF（Skp 1，culllin-1，F-box）泛素连接酶靶向其抑制剂I κ B α进行降解。I κ B α被含F盒结构域的蛋白β TrCP募集到SCF。在这里，我们表明，鼠痘的病原体，鼠痘病毒，编码四个F-盒含蛋白，EVM 002，EVM 005，EVM 154，和EVM 165，所有这些都含有锚蛋白（Ank）结构域。Ank/F-box蛋白抑制NF κ B B核转位，并且这种抑制依赖于F-box结构域。我们还证明了EVM 002、EVM 005、EVM 154和EVM 165阻止I κ B α降解，表明它们靶向SCF。这项研究确定了一种新的机制，其中鼠痘病毒抑制NF κ B。(C)2014爱思唯尔公司All rights reserved.
A notable feature of poxviruses is their ability to inhibit the antiviral response, including the nuclear factor kappa B (NF kappa B) pathway. NF kappa B is a transcription factor that is sequestered in the cytoplasm until cell stimulation, and relies on the SCF (Skp1, culllin-1, F-box) ubiquitin ligase to target its inhibitor, I kappa B alpha, for degradation. I kappa B alpha is recruited to the SCF by the F-box domain-containing protein beta TrCP. Here, we show that ectromelia virus, the causative agent of mousepox, encodes four F-box-containing proteins, EVM002, EVM005, EVM154, and EVM165, all of which contain Ankyrin (Ank) domains. The Ank/F-box proteins inhibit NF kappa B nuclear translocation, and this inhibition is dependent on the F-box domain. We also demonstrate that EVM002, EVM005, EVM154, and EVM165 prevent I kappa B alpha degradation, suggesting that they target the SCF. This study identifies a new mechanism by which ectromelia virus inhibits NF kappa B. (C) 2014 Elsevier Inc. All rights reserved.