Fas-associated Death Domain (FADD) and the E3 Ubiquitin-Protein Ligase TRIM21 Interact to Negatively Regulate Virus-induced Interferon Production

• DOI: 10.1074/jbc.m110.172288
• Publication Date: 2010-12-24T04:00:39Z
• Authors: Jennifer A. Young; Decha Sermwittaya...; Hee-Jung Kim; Suruchi Nandu; Namsil An; Hediye Erdjument-...; Paul Tempst; Laurent Coscoy; Astar Winoto
• Keywords: FADD; IRF7

The production of cytokines such as type I interferon (IFN) is an essential component innate immunity. Insufficient amounts lead to host sensitivity infection, whereas abundant cytokine can inflammation. A tight regulation is, thus, for homeostasis the immune system. IFN-α during RNA virus infection mediated by master transcription factor IRF7, which activated upon ubiquitination TRAF6 and phosphorylation IKKϵ TBK1 kinases. We found that Fas-associated death domain (FADD), first described apoptotic protein, involved in regulating through a novel interaction with TRIM21. TRIM21 member large family proteins impart ubiquitin modification onto its cellular targets. between FADD enhances ligase activity, together they cooperatively repress activation Sendai virus-infected cells. directly ubiquitinate affect status, interfere activity TRAF6. Conversely, reduction levels leads higher induction, IRF7 phosphorylation, lower titers infected conclude negatively regulate late pathway response viral infection.