Interference with nuclear factor kappaB signaling pathway by pathogen-encoded proteases: global and selective inhibition.
Interference with nuclear factor kappaB signaling pathway by pathogen-encoded proteases: global and selective inhibition.
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DOI：
10.1111/mmi.13245
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发表时间：
2016-02
影响因子：
3.6
通讯作者：
Wan F
中科院分区：
文献类型：
--
作者：
Hodgson A;Wan F
病原体已经进化出无数种方法来消除和操纵宿主对感染的反应。在涉及的各种机制中，病原体编码和有时宿主编码的蛋白酶是一类重要的毒力因子，它们通过沿着信号级联通路靶向关键蛋白，引起宿主反应的强烈变化。核因子κ b （NF-κB）信号通路是细胞的重要调控机制，控制着存活、免疫和增殖基因的表达。来自几乎所有类型病原体的蛋白酶已被证明可以在几乎所有水平上靶向和切割NF-κB信号通路的成员。本文综述了针对最丰富的NF-κB亚基p65的蛋白酶，以及蛋白酶介导的p65裂解对感染宿主细胞的免疫应答和存活的影响。在研究了各种蛋白酶干扰的例子后，很明显，由病原体驱动的蛋白水解加工产生的裂解片段应该进一步表征，以确定它们是否在细胞内具有新颖和独特的功能。p65的选择性靶向及其对基因转录的影响揭示了病原体急剧改变其微环境的独特机制，进一步的研究可能为对抗病原体的新疗法开辟新的机会。
Pathogens have evolved a myriad of ways to abrogate and manipulate the host response to infections. Of the various mechanisms involved, pathogen-encoded and sometimes host-encoded proteases are an important category of virulence factors that cause robust changes on the host response by targeting key proteins along signaling cascades. The nuclear factor kappaB (NF-κB) signaling pathway is a crucial regulatory mechanism for the cell, controlling the expression of survival, immune, and proliferation genes. Proteases from pathogens of almost all types have been demonstrated to target and cleave members of the NF-κB signaling pathway at nearly every level. This review provides discussion of proteases targeting the most abundant NF-κB subunit, p65, and the impact of protease-mediated p65 cleavage on the immune responses and survival of the infected host cell. After examining various examples of protease interference, it becomes evident that the cleavage fragments produced by pathogen-driven proteolytic processing should be further characterized to determine whether they have novel and unique functions within the cell. The selective targeting of p65 and its effect on gene transcription reveals unique mechanisms by which pathogens acutely alter their microenvironment and further research may open new opportunities for novel therapeutics to combat pathogens.
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影响因子：
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作者：
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通讯作者：
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Hardwidge PR