USP27X negatively regulates antiviral signaling by deubiquitinating RIG-I.,PLoS Pathogens

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USP27X negatively regulates antiviral signaling by deubiquitinating RIG-I.
PLoS Pathogens ( IF 5.5 ) Pub Date : 2020-02-06 , DOI: 10.1371/journal.ppat.1008293
Xinyue Tao _{1,

2} , Bei Chu _{1,

3} , Di Xin ₁ , Lin Li ₁ , Qinmiao Sun _{1,

2}

Affiliation

RIG-I plays important roles in pathogen sensing and activation of antiviral innate immune responses in response to RNA viruses. RIG-I-mediated signaling must be precisely controlled to maintain innate immune signaling homeostasis. Previous studies demonstrated that lysine 63 (K63)-linked polyubiquitination of RIG-I is vital for its activation, but the mechanisms through which RIG-I is deubiquitinated to control innate immune responses are not well understood. Here we identified USP27X as a negative regulator of antiviral signaling in response to RNA viruses through siRNA library screening. Further functional studies indicated that USP27X negatively modulated RIG-I-mediated antiviral signaling in a deubiquitinase-dependent manner. Mechanistically, we found that USP27X removed K63-linked polyubiquitin chains from RIG-I to negatively modulate type I interferon signaling. Collectively, these studies uncover a novel negative regulatory role of USP27X in targeting RIG-I to balance innate immune responses.

中文翻译：

USP27X 通过去泛素化 RIG-I 负向调节抗病毒信号。

RIG-I 在病原体感知和针对 RNA 病毒的抗病毒先天免疫反应激活中发挥着重要作用。必须精确控制 RIG-I 介导的信号传导以维持先天免疫信号传导稳态。先前的研究表明，RIG-I 赖氨酸 63 (K63) 连接的多聚泛素化对其激活至关重要，但 RIG-I 去泛素化以控制先天免疫反应的机制尚不清楚。在这里，我们通过 siRNA 文库筛选，确定 USP27X 是响应 RNA 病毒的抗病毒信号传导的负调节因子。进一步的功能研究表明，USP27X 以去泛素酶依赖性方式负向调节 RIG-I 介导的抗病毒信号传导。从机制上讲，我们发现 USP27X 从 RIG-I 中去除了 K63 连接的多聚泛素链，以负向调节 I 型干扰素信号传导。总的来说，这些研究揭示了 USP27X 在靶向 RIG-I 平衡先天免疫反应方面的新型负调节作用。

更新日期：2020-02-07

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