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牛痘诱导的表皮生长因子受体-MEK信号传导与抗凋亡蛋白F1L协同作用,在感染期间抑制细胞死亡。

Vaccinia-induced epidermal growth factor receptor-MEK signalling and the anti-apoptotic protein F1L synergize to suppress cell death during infection.

作者信息

Postigo Antonio, Martin Morag C, Dodding Mark P, Way Michael

机构信息

Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.

出版信息

Cell Microbiol. 2009 Aug;11(8):1208-18. doi: 10.1111/j.1462-5822.2009.01327.x. Epub 2009 Apr 22.

DOI:10.1111/j.1462-5822.2009.01327.x
PMID:19388902
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2730480/
Abstract

F1L is a functional Bcl-2 homologue that inhibits apoptosis at the mitochondria during vaccinia infection. However, the extent and timing of cell death during DeltaF1L virus infection suggest that additional viral effectors cooperate with F1L to limit apoptosis. Here we report that vaccinia growth factor (VGF), a secreted virulence factor, promotes cell survival independently of its role in virus multiplication. Analysis of single and double knockout viruses reveals that VGF acts synergistically with F1L to protect against cell death during infection. Cell survival in the absence of F1L is dependent on VGF activation of the epidermal growth factor receptor. Furthermore, signalling through MEK kinases is necessary and sufficient for VGF-dependent survival. We conclude that VGF stimulates an epidermal growth factor receptor-MEK-dependent pro-survival pathway that synergizes with F1L to counteract an infection-induced apoptotic pathway that predominantly involves the BH3-only protein Bad.

摘要

F1L是一种功能性Bcl-2同源物,在痘苗病毒感染期间可抑制线粒体的凋亡。然而,在DeltaF1L病毒感染期间细胞死亡的程度和时间表明,其他病毒效应因子与F1L协同作用以限制凋亡。在此我们报告,痘苗病毒生长因子(VGF),一种分泌型毒力因子,独立于其在病毒增殖中的作用促进细胞存活。对单基因敲除和双基因敲除病毒的分析表明,VGF与F1L协同作用以在感染期间防止细胞死亡。在缺乏F1L的情况下细胞存活依赖于表皮生长因子受体的VGF激活。此外,通过MEK激酶的信号传导对于VGF依赖性存活是必需且充分的。我们得出结论,VGF刺激一种表皮生长因子受体-MEK依赖性促存活途径,该途径与F1L协同作用以对抗主要涉及仅含BH3结构域蛋白Bad的感染诱导的凋亡途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fcc/2730480/58e980259a79/cmi0011-1208-f7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fcc/2730480/5f6ea6c79e20/cmi0011-1208-f2.jpg
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