eEF1Bγ is a positive regulator of NF-κB signaling pathway

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 (eEF1B gamma) activates NE-kappa B signaling pathway through targeting MAVS. GST-pull down and mass spectrometric analysis suggested that eEF1B gamma binds to the CARD domain of MAVS. The interaction and mitochondrial colocalization of eEF1B gamma and MAVS were further verified by co-immunoprecipitation (co-IP) and immunofluorescence microscopy assays. The dual-luciferase assays showed that ectopic expression of eEF1B gamma significantly promotes the activities of transcription factor NE-kappa B and promoters of downstream proinflammatory cytokines Interleukin-8 (IL-8) and Interleukin-6 (IL-6). eEF1B gamma 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 eEF1B gamma mediated ubiquitination. Collectively, these results demonstrated that eEF1By functions as a positive regulator of NF-kappa B signal by targeting MAVS for activation, which provides a new regulating mechanism of antiviral responses. (C) 2014 Elsevier Inc. All rights reserved.