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Enhancer of Zeste Homolog 2 Is a Negative Regulator of Mitochondria-Mediated Innate Immune Responses

J Immunol.. 2013-8; 
Shuai Chen, Chunjie Sheng, Dong Liu, Chen Yao, Shijuan Gao, Liping Song, Wei Jiang, Jiandong Li, Wenlin Huang. Institute of Microbiology, Chinese Academy of Sciences, No. 1 West Beichen Road, Beijing 100101, People's Republic of China.
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摘要

The intracellular RIG-I-like receptors recognize 5′-triphosphate viral genomic RNA and initiate the production of cytokines through mitochondria adaptor VISA. The regulation of this signal pathway is largely unknown. In this study, we report that the histone methyltransferase enhancer of zeste homolog 2 (EZH2) inhibits RIG-I signal pathway in an methyltransferase-independent manner. Knockdown EZH2 expression enhances VISA-induced activation of IFN-β promoter and NF-κB signaling. Cytosolic distributed EZH2 colocalizes with VISA and binds to its caspase recruitment domain (CARD), thus blocking its association with RIG-I. During the infection of influenza A virus (IAV) strain A/WSN/33 (WSN), EZH2 ... More

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