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首页> 外文期刊>Molecular and Cellular Biology >Kaposi's Sarcoma-Associated Herpesvirus K7 Protein Targets a Ubiquitin-Like/Ubiquitin-Associated Domain-Containing Protein To Promote Protein Degradation
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Kaposi's Sarcoma-Associated Herpesvirus K7 Protein Targets a Ubiquitin-Like/Ubiquitin-Associated Domain-Containing Protein To Promote Protein Degradation

机译：卡波西氏肉瘤相关疱疹病毒K7蛋白靶向泛素样/泛素相关域蛋白，以促进蛋白质降解

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Pathogens exploit host machinery to establish an environment that favors their propagation. Because of their pivotal roles in cellular physiology, protein degradation pathways are common targets for viral proteins. Protein-linking integrin-associated protein and cytoskeleton 1 (PLIC1), also called ubiquilin, contains an amino-terminal ubiquitin-like (UBL) domain and a carboxy-terminal ubiquitin-associated (UBA) domain. PLIC1 is proposed to function as a regulator of the ubiquitination complex and proteasome machinery. Kaposi's sarcoma-associated herpesvirus (KSHV) contains a small membrane protein, K7, that protects cells from apoptosis induced by various stimuli. We report here that cellular PLIC1 is a K7-interacting protein and that the central hydrophobic region of K7 and the carboxy-terminal UBA domain of PLIC1 are responsible for their interaction. Cellular PLIC1 formed a dimer and bound efficiently to polyubiquitinated proteins through its carboxy-terminal UBA domain, and this activity correlated with its ability to stabilize cellular IκB protein. In contrast, K7 interaction prevented PLIC1 from forming a dimer and binding to polyubiquitinated proteins, leading to the rapid degradation of IκB. Furthermore, K7 expression promoted efficient degradation of the p53 tumor suppressor, resulting in inhibition of p53-mediated apoptosis. These results indicate that KSHV K7 targets a regulator of the ubiquitin- and proteasome-mediated degradation machinery to deregulate cellular protein turnover, which potentially provides a favorable environment for viral reproduction.
机译：病原体利用宿主机器建立有利于其繁殖的环境。由于其在细胞生理学中的关键作用，蛋白质降解途径是病毒蛋白质的常见靶标。蛋白质连接整合素相关蛋白和细胞骨架1（PLIC1），也称为泛蛋白，包含一个氨基末端泛素样（UBL）域和一个羧基末端泛素相关（UBA）域。有人提议PLIC1作为泛素复合体和蛋白酶体机制的调节剂。卡波济氏肉瘤相关疱疹病毒（KSHV）含有一种小的膜蛋白K7，可保护细胞免受各种刺激诱导的细胞凋亡。我们在这里报告细胞PLIC1是一种K7相互作用蛋白，并且K7的中央疏水区和PLIC1的羧基末端UBA结构域负责它们的相互作用。细胞PLIC1形成二聚体，并通过其羧基末端UBA结构域与多聚泛素化蛋白有效结合，这种活性与其稳定细胞IκB蛋白的能力有关。相反，K7相互作用阻止PLIC1形成二聚体并与多泛素化蛋白结合，从而导致IκB迅速降解。此外，K7表达促进p53肿瘤抑制因子的有效降解，从而抑制p53介导的细胞凋亡。这些结果表明KSHV K7靶向于遍在蛋白和蛋白酶体介导的降解机制的调节剂，以调节细胞蛋白更新，这可能为病毒繁殖提供有利的环境。

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