The ubiquitin-specific protease 17 is involved in virus-triggered type I IFN signaling
The ubiquitin-specific protease 17 is involved in virus-triggered type I IFN signaling
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泛素特异性蛋白酶 17 参与病毒触发的 I 型 IFN 信号传导
DOI：
10.1038/cr.2010.41
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发表时间：
2010-07-01
期刊：
影响因子：
44.1
通讯作者：
Shu, Hong-Bing
中科院分区：
文献类型：
--
作者：
Chen, Rui;Zhang, Lu;Shu, Hong-Bing
病毒感染启动一系列信号级联反应，激活转录因子核因子kappa B和干扰素调节因子3，它们共同诱导I型干扰素和其他细胞因子基因的转录。在此，我们报道了病毒诱导的Rig-I和黑色素瘤分化相关蛋白-5(MDA5)介导的I型干扰素信号转导所必需的去泛素化酶泛素特异性蛋白17(USP17)。内源性USP17的敲除可抑制病毒、胞浆多聚(I：C)和多聚(da：dt)诱导的干扰素-β启动子的激活和细胞抗病毒反应。我们进一步发现，USP17的敲除抑制了RIG-I和MDA5诱导的干扰素-β启动子的激活，但不抑制下游激活剂诱导的激活，这与RIG-I和MDA5泛素化水平的增加有关。综上所述，我们的发现表明，USP17通过RIG-I和MDA5的去泛素化来调节病毒诱导的I型干扰素信号。
Viral infection initiates a series of signaling cascades that activate the transcription factors nuclear factor kappa B and interferon regulatory factor 3, which collaborate to induce transcription of genes for type I interferons (IFNs) and other cytokines. Here we report that the deubiquitinating enzyme ubiquitin-specific protease 17 (USP17) is required for virus-induced RIG-I-and melanoma differentiation-associated protein-5 (MDA5)-mediated type I IFN signaling. Knockdown of endogenous USP17 inhibited virus-, cytoplasmic poly (I: C)-and poly (dA: dT)-induced activation of the IFN-β promoter and cellular antiviral responses. We further found that knockdown of USP17 inhibited RIG-I-and MDA5-induced but not downstream activator-induced activation of the IFN-β promoter, which was correlated with an increase in ubiquitination levels of RIG-I and MDA5. Taken together, our findings suggest that USP17 functions through deubiquitination of RIG-I and MDA5 to regulate virus-induced type I IFN signaling.