Mitochondria–Nucleus Shuttling FK506-Binding Protein 51 Interacts with TRAF Proteins and Facilitates the RIG-I-Like Receptor-Mediated Expression of Type I IFN
dc.contributor.author | Akiyama, Taishin | |
dc.contributor.author | Shiraishi, Takuma | |
dc.contributor.author | Qin, Junwen | |
dc.contributor.author | Konno, Hiroyasu | |
dc.contributor.author | Akiyama, Nobuko | |
dc.contributor.author | Shinzawa, Miho | |
dc.contributor.author | Miyauchi, Maki | |
dc.contributor.author | Takizawa, Nobukazu | |
dc.contributor.author | Yanai, Hiromi | |
dc.contributor.author | Ohashi, Hiroyuki | |
dc.contributor.author | Miyamoto-Sato, Etsuko | |
dc.contributor.author | Yanagawa, Hiroshi | |
dc.contributor.author | Yong, Weidong | |
dc.contributor.author | Shou, Weinian | |
dc.contributor.author | Inoue, Jun-ichiro | |
dc.contributor.department | Pediatrics, School of Medicine | |
dc.date.accessioned | 2025-04-08T11:59:40Z | |
dc.date.available | 2025-04-08T11:59:40Z | |
dc.date.issued | 2014-05-01 | |
dc.description.abstract | Virus-derived double-stranded RNAs (dsRNAs) are sensed in the cytosol by retinoic acid-inducible gene (RIG)-I-like receptors (RLRs). These induce the expression of type I IFN and proinflammatory cytokines through signaling pathways mediated by the mitochondrial antiviral signaling (MAVS) protein. TNF receptor-associated factor (TRAF) family proteins are reported to facilitate the RLR-dependent expression of type I IFN by interacting with MAVS. However, the precise regulatory mechanisms remain unclear. Here, we show the role of FK506-binding protein 51 (FKBP51) in regulating the dsRNA-dependent expression of type I IFN. The binding of FKBP51 to TRAF6 was first identified by "in vitro virus" selection and was subsequently confirmed with a coimmunoprecipitation assay in HEK293T cells. The TRAF-C domain of TRAF6 is required for its interaction, although FKBP51 does not contain the consensus motif for interaction with the TRAF-C domain. Besides TRAF6, we found that FKBP51 also interacts with TRAF3. The depletion of FKBP51 reduced the expression of type I IFN induced by dsRNA transfection or Newcastle disease virus infection in murine fibroblasts. Consistent with this, the FKBP51 depletion attenuated dsRNA-mediated phosphorylations of IRF3 and JNK and nuclear translocation of RelA. Interestingly, dsRNA stimulation promoted the accumulation of FKBP51 in the mitochondria. Moreover, the overexpression of FKBP51 inhibited RLR-dependent transcriptional activation, suggesting a scaffolding function for FKBP51 in the MAVS-mediated signaling pathway. Overall, we have demonstrated that FKBP51 interacts with TRAF proteins and facilitates the expression of type I IFN induced by cytosolic dsRNA. These findings suggest a novel role for FKBP51 in the innate immune response to viral infection. | |
dc.eprint.version | Final published version | |
dc.identifier.citation | Akiyama T, Shiraishi T, Qin J, et al. Mitochondria-nucleus shuttling FK506-binding protein 51 interacts with TRAF proteins and facilitates the RIG-I-like receptor-mediated expression of type I IFN. PLoS One. 2014;9(5):e95992. Published 2014 May 1. doi:10.1371/journal.pone.0095992 | |
dc.identifier.uri | https://hdl.handle.net/1805/46879 | |
dc.language.iso | en_US | |
dc.publisher | Public Library of Science | |
dc.relation.isversionof | 10.1371/journal.pone.0095992 | |
dc.relation.journal | PLoS One | |
dc.rights | Attribution 4.0 International | en |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | PMC | |
dc.subject | Newcastle disease virus | |
dc.subject | Gene expression regulation | |
dc.subject | Mitochondria | |
dc.subject | Protein interaction mapping | |
dc.title | Mitochondria–Nucleus Shuttling FK506-Binding Protein 51 Interacts with TRAF Proteins and Facilitates the RIG-I-Like Receptor-Mediated Expression of Type I IFN | |
dc.type | Article |