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Regulation of MDA5-MAVS Antiviral Signaling Axis by TRIM25 through TRAF6-Mediated NF-κB Activation

  • Lee, Na-Rae (Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University) ;
  • Kim, Hye-In (Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University) ;
  • Choi, Myung-Soo (Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University) ;
  • Yi, Chae-Min (Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University) ;
  • Inn, Kyung-Soo (Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University)
  • Received : 2015.03.17
  • Accepted : 2015.07.01
  • Published : 2015.09.30

Abstract

Tripartite motif protein 25 (TRIM25), mediates K63-linked polyubiquitination of Retinoic acid inducible gene I (RIG-I) that is crucial for downstream antiviral interferon signaling. Here, we demonstrate that TRIM25 is required for melanoma differentiation-associated gene 5 (MDA5) and MAVS mediated activation of NF-${\kappa}B$ and interferon production. TRIM25 is required for the full activation of NF-${\kappa}B$ at the downstream of MAVS, while it is not involved in IRF3 nuclear translocation. Mechanical studies showed that TRIM25 is involved in TRAF6-mediated NF-${\kappa}B$ activation. These collectively indicate that TRIM25 plays an additional role in RIG-I/MDA5 signaling other than RIG-I ubiquitination via activation of NF-${\kappa}B$.

Acknowledgement

Supported by : National Research Foundation of Korea (NRF)

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