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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.
Pubmed ID: 24788966 RIS Download
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THIS RESOURCE IS NO LONGER IN SERVICE. Documented on September 23,2022. Integrated database of experiment data generated by participating research institutes and public databases relating to: 1) transcription starting position of human genes in the human genome, 2) conjunction to control region on transcriptional factors and the human genome 3) protein-protein interaction with a central focus on transcription factors organized for use in genome level research. Gene Search is the function to search the integrated database by using keywords and public IDs. The search results can be visualized by: * Genome Explorer : provides annotation of landmarks (genes, transcription start sites, etc.) aligned in accordance with their genome locations. * PPI Network : provides a graphical view of protein-protein interaction (PPI) network from the experimental data generated under the project and the public datasets. * Expression Profile : clusters genes by expression pattern and display the result with heatmap. The function provides genes which have relation of coregulation and anti-coregulation. * Comparison Viewer : This function gives the view to compare the genomic regions between human and mouse homologous genes. The viewer shows the distribution of transcription start sites (TSS) as the way of separable by tissues or time points with other landmarks on genome region. * Gene Stock : This is the function to save the gene list that you are interested until the session is closed.
View all literature mentionsCell line NCTC clone 929 is a Spontaneously immortalized cell line with a species of origin Mus musculus
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
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