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SnapShot: The Unfolded Protein Response

The Scripps Research Institute, La Jolla, CA, USA
Cell (Impact Factor: 32.24). 02/2010; 140(4):590-590.e2. DOI: 10.1016/j.cell.2010.02.006
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    • "An EVOO secoiridoid-rich extract upregulated the transcriptional expression of the DNAJA4 and DNAJC3 genes, which encodes the ER-localized DNAJ family of proteins[110]. The induced transcription of DNAJ genes is part of the UPR111112113114. The ability of secoiridoids from EVOO to upregulate a set of genes involved in the ER stress response to accumulation of unfolded proteins may appear to conflict with the demonstrated ability of these compounds to strongly inhibit the growth of highly aggressive breast cancer cells[53,115]. "
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    • "Once activated, the three mammalian ER-stress transducers act in a coordinated manner to restore ER homeostasis, not only by increasing the expression of genes encoding chaperones – i.e. the ancestral branch of the UPR – but also by reducing global protein synthesis, which constitutes a rapid adaptive response to stress (Fig. 2). This is mediated by PERK, which, in response to the folding perturbation in the ER or simply when the folding supply does not match the demand, phosphorylates the α subunit of eukaryotic translation initiation factor 2 (eIF2α) on residue Ser51 to reduce translation initiation (Wiseman et al., 2010; Cao and Kaufman, 2012). This represents a first line of defense against the threat of protein misfolding. "
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    • "In response to disturbed endoplasmic reticulum (ER) homeostasis, signaling pathways known as unfolded protein response (UPR) signaling are induced to restore the protein folding capacity of ER. These signaling pathways are transduced by three sensor proteins PERK, IRE1α, and ATF6α to restore protein folding in a translational-and transcriptional-dependent manner (Wiseman et al., 2010). In addition to this fundamental chaperon function, UPR is found to be associated with the pathogenesis of various diseases/disorders such as inflammation , obesity, diabetes, atherosclerosis and neurodegeneration (Cnop et al., 2012; Wang and Kaufman, 2012; Zhang, 2010; Zhang and Kaufman, 2008). "
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