Mitochondria-nucleus shuttling FK506-binding protein 51 interacts with TRAF proteins and facilitates the RIG-I-like receptor-mediated expression of type I IFN

Taishin Akiyama, Takuma Shiraishi, Junwen Qin, Hiroyasu Konno, Nobuko Akiyama, Miho Shinzawa, Maki Miyauchi, Nobukazu Takizawa, Hiromi Yanai, Hiroyuki Ohashi, Etsuko Miyamoto-Sato, Hiroshi Yanagawa, Weidong Yong, Weinian Shou, Jun Ichiro Inoue

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article numbere95992
JournalPLoS One
Volume9
Issue number5
DOIs
StatePublished - May 1 2014

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Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Tacrolimus Binding Proteins
Mitochondria
retinoic acid
Tretinoin
binding proteins
mitochondria
Genes
receptors
double-stranded RNA
TNF Receptor-Associated Factor 6
Proteins
genes
proteins
Viruses
Antiviral Agents
Virus Diseases
TNF Receptor-Associated Factor 3
Newcastle disease virus
viruses

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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Mitochondria-nucleus shuttling FK506-binding protein 51 interacts with TRAF proteins and facilitates the RIG-I-like receptor-mediated expression of type I IFN. / Akiyama, Taishin; Shiraishi, Takuma; Qin, Junwen; Konno, Hiroyasu; Akiyama, Nobuko; Shinzawa, Miho; Miyauchi, Maki; Takizawa, Nobukazu; Yanai, Hiromi; Ohashi, Hiroyuki; Miyamoto-Sato, Etsuko; Yanagawa, Hiroshi; Yong, Weidong; Shou, Weinian; Inoue, Jun Ichiro.

In: PLoS One, Vol. 9, No. 5, e95992, 01.05.2014.

Research output: Contribution to journalArticle

Akiyama, T, Shiraishi, T, Qin, J, Konno, H, Akiyama, N, Shinzawa, M, Miyauchi, M, Takizawa, N, Yanai, H, Ohashi, H, Miyamoto-Sato, E, Yanagawa, H, Yong, W, Shou, W & Inoue, JI 2014, '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, vol. 9, no. 5, e95992. https://doi.org/10.1371/journal.pone.0095992
Akiyama, Taishin ; Shiraishi, Takuma ; Qin, Junwen ; Konno, Hiroyasu ; Akiyama, Nobuko ; Shinzawa, Miho ; Miyauchi, Maki ; Takizawa, Nobukazu ; Yanai, Hiromi ; Ohashi, Hiroyuki ; Miyamoto-Sato, Etsuko ; Yanagawa, Hiroshi ; Yong, Weidong ; Shou, Weinian ; Inoue, Jun Ichiro. / Mitochondria-nucleus shuttling FK506-binding protein 51 interacts with TRAF proteins and facilitates the RIG-I-like receptor-mediated expression of type I IFN. In: PLoS One. 2014 ; Vol. 9, No. 5.
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AU - Akiyama, Taishin

AU - Shiraishi, Takuma

AU - Qin, Junwen

AU - Konno, Hiroyasu

AU - Akiyama, Nobuko

AU - Shinzawa, Miho

AU - Miyauchi, Maki

AU - Takizawa, Nobukazu

AU - Yanai, Hiromi

AU - Ohashi, Hiroyuki

AU - Miyamoto-Sato, Etsuko

AU - Yanagawa, Hiroshi

AU - Yong, Weidong

AU - Shou, Weinian

AU - Inoue, Jun Ichiro

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