PI3K Signaling Regulates Rapamycin-Insensitive Translation Initiation Complex Formation in Vaccinia Virus-Infected Cells
PI3K Signaling Regulates Rapamycin-Insensitive Translation Initiation Complex Formation in Vaccinia Virus-Infected Cells
复制标题
DOI：
10.1128/jvi.02284-08
复制
发表时间：
2009-04-15
影响因子：
5.4
通讯作者：
Walsh, Derek
中科院分区：
文献类型：
--
作者：
Zaborowska, Izabela;Walsh, Derek
牛痘病毒（VV）如何调节宿主翻译起始复合物eIF 4F的组装仍不清楚。在这里，我们表明VV激活宿主PI 3 K以刺激下游哺乳动物雷帕霉素靶蛋白（mTOR），这是一种使翻译阻遏物4 E-BP 1失活的激酶。然而，尽管mTOR抑制剂雷帕霉素抑制VV诱导的4 E-BP 1失活，但它未能抑制eIF 4F组装。相反，VV感染细胞中的PI 3 K抑制增加了低磷酸化4 E-BP 1的丰度，并破坏了eIF 4F复合物的形成。因此，PI 3 K信号传导在VV感染期间调节蛋白质产生中起关键作用，至少部分通过控制4 E-BP 1的丰度和活性。
How vaccinia virus (VV) regulates assembly of the host translation initiation complex eIF4F remains unclear. Here, we show that VV activated host PI3K to stimulate downstream mammalian target of rapamycin (mTOR), a kinase that inactivates the translational repressor 4E-BP1. However, although the mTOR inhibitor rapamycin suppressed VV-induced inactivation of 4E-BP1, it failed to inhibit eIF4F assembly. In contrast, PI3K inhibition in VV-infected cells increased the abundance of hypophosphorylated 4E-BP1 and disrupted eIF4F complex formation. PI3K signaling, therefore, plays a critical role in regulating protein production during VV infection, at least in part by controlling the abundance and activity of 4E-BP1.