Negative regulation of RIG-I-mediated antiviral signaling by TRK-fused gene (TFG) protein

作者：Lee Na Rae; Shin Han Bo; Kim Hye In; Choi Myung Soo; Inn Kyung Soo^*

来源：Biochemical and Biophysical Research Communications, 2013, 437(1): 168-172.

DOI：10.1016/j.bbrc.2013.06.061

• RIG-I
• TRIM25
• Interferon
• TRK-fused gene protein
• TFG
• Antiviral signaling

RIG-I (retinoic acid inducible gene I)-mediated antiviral signaling serves as the first line of defense against viral infection. Upon detection of viral RNA, RIG-I undergoes TRIM25 (tripartite motif protein 25)-mediated K63-linked ubiquitination, leading to type I interferon (IFN) production. In this study, we demonstrate that TRK-fused gene (TFG) protein, previously identified as a TRIM25-interacting protein, binds TRIM25 upon virus infection and negatively regulates RIG-I-mediated type-I IFN signaling. RIG-I-mediated IFN production and nuclear factor (NF)-kappa B signaling pathways were upregulated by the suppression of TFG expression. Furthermore, vesicular stomatitis virus (VSV) replication was significantly inhibited by small inhibitory hairpin RNA (shRNA)-mediated knockdown of TFG, supporting the suppressive role of TFG in RIG-I-mediated antiviral signaling. Interestingly, suppression of TFG expression increased not only RIG-I-mediated signaling but also MAVS (mitochondrial antiviral signaling protein)-induced signaling, suggesting that TFG plays a pivotal role in negative regulation of RNA-sensing, RIG-I-like receptor (RLR) family signaling pathways.

• 出版日期2013-7-19