BAG6 negatively regulates the RLR signaling pathway by targeting VISA/MAVS.
The virus-induced signaling adaptor protein VISA (also known as MAVS, ISP-1, Cardif) is a critical adaptor protein in the innate immune response to RNA virus infection. Upon viral infection, VISA self-aggregates to form a sizeable prion-like complex and recruits downstream signal components for signal transduction. Here, we discover that BAG6 ... (BCL2-associated athanogene 6, formerly BAT3 or Scythe) is an essential negative regulator in the RIG-I-like receptor signaling pathway. BAG6 inhibits the aggregation of VISA by promoting the K48-linked ubiquitination and specifically attenuates the recruitment of TRAF2 by VISA to inhibit RLR signaling. The aggregation of VISA and the interaction of VISA and TRAF2 are enhanced in BAG6-deficient cell lines after viral infection, resulting in the enhanced transcription level of downstream antiviral genes. Our research shows that BAG6 is a critical regulating factor in RIG-I/VISA-mediated innate immune response by targeting VISA.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Humans, Mice, Molecular Chaperones, Nuclear Proteins, Signal Transduction, TNF Receptor-Associated Factor 2, Ubiquitin-Protein Ligases, Ubiquitination, Virus Diseases
Adaptor Proteins, Signal Transducing, Animals, Humans, Mice, Molecular Chaperones, Nuclear Proteins, Signal Transduction, TNF Receptor-Associated Factor 2, Ubiquitin-Protein Ligases, Ubiquitination, Virus Diseases
Front Immunol
Date: Sep. 02, 2022
PubMed ID: 36045679
View in: Pubmed Google Scholar
Download Curated Data For This Publication
239707
Switch View:
- Interactions 5