BAG6 negatively regulates the RLR signaling pathway by targeting VISA/MAVS.

Abstract

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.

• Authors: Jing-Ping Huang, Jing Li, Yan-Ping Xiao, Liang-Guo Xu
• Journal: Frontiers in immunology (Front Immunol) Vol. 13 Pg. 972184 ( 2022) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 36045679 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Huang, Li, Xiao and Xu.

Chemical References

• Adaptor Proteins, Signal Transducing
• BAG6 protein, human
• Bag6 protein, mouse
• Molecular Chaperones
• Nuclear Proteins
• TNF Receptor-Associated Factor 2
• VISA protein, mouse
• Ubiquitin-Protein Ligases

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Animals
• Humans
• Mice
• Molecular Chaperones (genetics, metabolism)
• Nuclear Proteins (metabolism)
• Signal Transduction
• TNF Receptor-Associated Factor 2 (metabolism)
• Ubiquitin-Protein Ligases (metabolism)
• Ubiquitination
• Virus Diseases