REUL is a novel E3 ubiquitin ligase and stimulator of retinoic-acid-inducible gene-I.
REUL is a novel E3 ubiquitin ligase and stimulator of retinoic-acid-inducible gene-I.
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DOI：
10.1371/journal.pone.0005760
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发表时间：
2009-06-01
期刊：
影响因子：
3.7
通讯作者：
Chen DY
中科院分区：
文献类型：
--
作者：
Gao D;Yang YK;Wang RP;Zhou X;Diao FC;Li MD;Zhai ZH;Jiang ZF;Chen DY
RIG-I和MDA 5是识别不同种类病毒RNA的细胞质传感器，导致转录因子IRF 3和NF-κB的激活，其协作诱导I型干扰素。在这项研究中，我们确定了REUL，环指蛋白，作为一个特定的RIG-I相互作用蛋白。REUL通过其PRY和SPRY结构域与RIG-I相关，但与MDA 5无关。REUL的过表达有力地增强了RIG-I介导的下游信号传导和抗病毒活性，但不增强MDA 5介导的下游信号传导和抗病毒活性。相反，REUL的RING结构域缺失突变体抑制仙台病毒（SV）诱导的IFN-β启动子激活，但不抑制胞质polyI：C诱导的IFN-β启动子激活。通过RNAi敲低内源性REUL抑制SV触发的IFN-β表达，并且还增加VSV复制。全长RIG-I，但不是RIG-I的CARD结构域缺失突变体，经历了由REUL诱导的泛素化。RIG-I CARD结构域的154、164和172位赖氨酸残基对于有效的REUL介导的泛素化以及RIG-I诱导IFN-β启动子活化的能力至关重要。这些发现表明，REUL是RIG-I的E3泛素连接酶，并特异性地刺激RIG-I介导的先天性抗病毒活性。
RIG-I and MDA5 are cytoplasmic sensors that recognize different species of viral RNAs, leads to activation of the transcription factors IRF3 and NF-κB, which collaborate to induce type I interferons. In this study, we identified REUL, a RING-finger protein, as a specific RIG-I-interacting protein. REUL was associated with RIG-I, but not MDA5, through its PRY and SPRY domains. Overexpression of REUL potently potentiated RIG-I-, but not MDA5-mediated downstream signalling and antiviral activity. In contrast, the RING domain deletion mutant of REUL suppressed Sendai virus (SV)-induced, but not cytoplasmic polyI:C-induced activation of IFN-β promoter. Knockdown of endogenous REUL by RNAi inhibited SV-triggered IFN-β expression, and also increased VSV replication. Full-length RIG-I, but not the CARD domain deletion mutant of RIG-I, underwent ubiquitination induced by REUL. The Lys 154, 164, and 172 residues of the RIG-I CARD domain were critical for efficient REUL-mediated ubiquitination, as well as the ability of RIG-I to induce activation of IFN-β promoter. These findings suggest that REUL is an E3 ubiquitin ligase of RIG-I and specifically stimulates RIG-I-mediated innate antiviral activity.
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影响因子：
56.9
作者：
Pichlmair, Andreas;Schulz, Oliver;Sousa, Caetano Reis E.
通讯作者：
Sousa, Caetano Reis E.
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通讯作者：
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作者：
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通讯作者：
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