eEF1Bgamma is a positive regulator of NF-small ka, CyrillicB signaling pathway----中国科学院微生物研究所

科研成果

论文题目:	eEF1Bgamma is a positive regulator of NF-small ka, CyrillicB signaling pathway
作者:	Liu Dong, Sheng Chunjie, Gao Shijuan, Jiang Wei, Li Jiandong, Yao Chen, Chen Huiming, Wu Jiaoxiang, Chen Shuai, Huang Wenlin
联系作者:	Chen Shuai, Huang Wenlin
刊物名称:	Biochem Biophys Res Commun
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年份:	2014
影响因子:	2.5
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摘要:	Mitochondrial antiviral-signaling protein (MAVS), as a critical adaptor of RIG-I signaling, bridges viral RNA recognition and downstream signal activation. However, the regulating mechanisms of MAVS are not well understood. In this study, we demonstrated that eukaryotic elongation factor 1B gamma (eEF1Bgamma) activates NF-small ka, CyrillicB signaling pathway through targeting MAVS. GST-pull down and mass spectrometric analysis suggested that eEF1Bgamma binds to the CARD domain of MAVS. The interaction and mitochondrial colocalization of eEF1Bgamma and MAVS were further verified by co-immunoprecipitation (co-IP) and immunofluorescence microscopy assays. The dual-luciferase assays showed that ectopic expression of eEF1Bgamma significantly promotes the activities of transcription factor NF-small ka, CyrillicB and promoters of downstream proinflammatory cytokines Interleukin-8 (IL-8) and Interleukin-6 (IL-6). eEF1Bgamma increases the abundance of MAVS by promoting its K63-linked polyubiquitination and attenuating its K48-linked polyubiquitination. Besides, proline-rich (Pro) region and CARD domain of MAVS are indispensable for the process of eEF1Bgamma mediated ubiquitination. Collectively, these results demonstrated that eEF1Bgamma functions as a positive regulator of NF-small ka, CyrillicB signal by targeting MAVS for activation, which provides a new regulating mechanism of antiviral responses.