FIP200 is essential for RIG-I-mediated innate immune signaling

• DOI: 10.4049/jimmunol.204.supp.70.3
• Publication Date: 2023-01-01T14:48:52Z
• Authors: Shitao Li; Lingyan Wang; Kun Song; Girish Patil; Wenzhuo Hao; Yakun Wu
• Keywords: RIG-I; MDA5

Abstract Retinoic acid-inducible gene I (RIG-I) is a cytosolic sensor for recognition of viral double-stranded RNA (dsRNA) and 5′ triphosphate RNA, which induces robust production type interferon (IFN). Following recognition, the caspase activation recruitment domain (CARD) RIG-I released from repressor subsequently oligomerized to activate downstream signal cascades. Although these sequential steps are well established; however, regulatory mechanism not elucidated. In this study, we found that FAK family kinase-interacting protein 200 kDa (FIP200) interacted with CARD RIG-I. Ectopic expression FIP200 activated By contrast, knockout impaired signaling, but other innate immune signaling pathways, in fibroblasts macrophages. vivo study showed mice were more susceptible VSV, HSV-1, infection due reduced responses, including IFN. Mechanistic analyses promoted release by competing Furthermore, formed dimers via its C-terminal tail, facilitated oligomerization subsequent activation. Taken together, our defines as new molecule facilities