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Bluetongue virus (BTV), a complex double-stranded segmented RNA virus, has been found to initiate cellular autophagy for its own benefit. Here, with a view to understanding the underlying mechanisms, we first systematically dissected the exact signaling network in BTV-induced autophagy. We found that the activity of mTOR, a crucial pivot, was inhibited by BTV1 infection, subsequently leading to downstream p70S6K suppression and autophagy initiation. We then explored the upstream regulators of mTOR and analyzed their activities via a series of assays. We found BTV1-induced autophagy to be independent of the ERK1/2 signaling pathway. However, the BTV1-induced inhibition of PI3K/Akt was found to be partially responsible for mTOR inactivation and subsequent autophagy initiation. Furthermore, we found unexpectedly that AMPK seemed to play a more important role in BTV1-induced autophagy. Elevated [Ca(2+)]cyto-mediated activation of CaMKKβ exactly managed the activation of AMPK, which then positively regulated autophagy through suppressing mTOR. We must emphasize that TSC2 is a fatal mediator between upstream Akt or AMPK and downstream mTOR through its phosphorylation. Taken together, our data suggested that the BTV1-induced inhibition of the Akt-TSC2-mTOR pathway and the upregulation of the AMPK-TSC2-mTOR pathway both contributed to autophagy initiation and further favored virus replication.
Pubmed ID: 26976147 RIS Download
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A research tool company focused on the creation of the largest commercial collection of full-length human cDNAs in a standard expression vector. The availability of the complete human genome sequence and the subsequent development of genome-based tools have enabled the identification of relevant drug targets through system biology approaches. OriGene''s vision is to prepare comprehensive, genome wide research tools and technology platforms to enable scientists to study complete biological pathways, thus enabling a better understanding of disease mechanisms including cancer and stem cell research. OriGene Technologies uses high-throughput, genome wide approach to develop products for pharmaceutical, biotechnology, and academic research. Their flagship product is the cDNA clone collection, a searchable gene bank of over 30,000 human full-length TrueClone cDNA collection and over 25,000 TrueORF cDNA clones. From their TrueORF cDNA clones, they have developed the largest offering of full length human proteins expressed in mammalian cells, ideal for functional studies. Their TrueMAB project develops mouse monoclonal antibodies against protein antigens with the goal to develop protein assays for every human protein. They also offer complete molecular biology services from codon optimization, gene synthesis, protein expression and assay development. In addition, they offer unique gene expression products such as TissueScan cancer tissue qPCR arrays and tissue biorepository for biomarker discovery and validation.
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