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.authorAkiyama, Taishin
dc.contributor.authorShiraishi, Takuma
dc.contributor.authorQin, Junwen
dc.contributor.authorKonno, Hiroyasu
dc.contributor.authorAkiyama, Nobuko
dc.contributor.authorShinzawa, Miho
dc.contributor.authorMiyauchi, Maki
dc.contributor.authorTakizawa, Nobukazu
dc.contributor.authorYanai, Hiromi
dc.contributor.authorOhashi, Hiroyuki
dc.contributor.authorMiyamoto-Sato, Etsuko
dc.contributor.authorYanagawa, Hiroshi
dc.contributor.authorYong, Weidong
dc.contributor.authorShou, Weinian
dc.contributor.authorInoue, Jun-ichiro
dc.contributor.departmentPediatrics, School of Medicine
dc.date.accessioned2025-04-08T11:59:40Z
dc.date.available2025-04-08T11:59:40Z
dc.date.issued2014-05-01
dc.description.abstractVirus-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.versionFinal published version
dc.identifier.citationAkiyama 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.urihttps://hdl.handle.net/1805/46879
dc.language.isoen_US
dc.publisherPublic Library of Science
dc.relation.isversionof10.1371/journal.pone.0095992
dc.relation.journalPLoS One
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourcePMC
dc.subjectNewcastle disease virus
dc.subjectGene expression regulation
dc.subjectMitochondria
dc.subjectProtein interaction mapping
dc.titleMitochondria–Nucleus Shuttling FK506-Binding Protein 51 Interacts with TRAF Proteins and Facilitates the RIG-I-Like Receptor-Mediated Expression of Type I IFN
dc.typeArticle
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