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首页> 外文期刊>Nature immunology >PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection.
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PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection.

机译:PARP9-DTX3L泛素连接酶靶向宿主组蛋白H2BJ和病毒3C蛋白酶,以增强干扰素信号传导并控制病毒感染。

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摘要

Enhancing the response to interferon could offer an immunological advantage to the host. In support of this concept, we used a modified form of the transcription factor STAT1 to achieve hyper-responsiveness to interferon without toxicity and markedly improve antiviral function in transgenic mice and transduced human cells. We found that the improvement depended on expression of a PARP9-DTX3L complex with distinct domains for interaction with STAT1 and for activity as an E3 ubiquitin ligase that acted on host histone H2BJ to promote interferon-stimulated gene expression and on viral 3C proteases to degrade these proteases via the immunoproteasome. Thus, PARP9-DTX3L acted on host and pathogen to achieve a double layer of immunity within a safe reserve in the interferon signaling pathway.
机译:增强对干扰素的反应可以为宿主提供免疫学优势。为了支持该概念,我们使用了转录因子STAT1的修饰形式,以实现对干扰素的高反应性而无毒性,并显着改善了转基因小鼠和转导的人类细胞中的抗病毒功能。我们发现,这种改善取决于PARP9-DTX3L复合物的表达,该复合物具有与STAT1相互作用和作为E3泛素连接酶的活性的不同域,该E3泛素连接酶作用于宿主组蛋白H2BJ,以促进干扰素刺激的基因表达,并依赖病毒3C蛋白酶降解这些蛋白蛋白酶通过免疫蛋白酶体。因此,PARP9-DTX3L对宿主和病原体起作用,以在干扰素信号传导途径的安全储备内实现双层免疫。

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