Abstract
The endoplasmic reticulum (ER) is the organelle where approximately one-third of all proteins are folded and assembled into higher molecular weight structures before transit to their final destinations. In addition, the ER is the major calcium storage organelle in the cell and it responds to stimuli to release calcium into the cytosol in a regulated manner. The ER is exquisitely sensitive to alterations in homeostasis. Upon disruption of ER function, signals are initiated that propagate both adaptive and cell death responses. A number of stresses such as altered or inhibition of asparagine-linked glycosylation, reduction of disulfide bonds, expression of mutant or even some wild-type proteins, or glucose deprivation activate signaling pathways that are collectively termed the unfolded protein response (UPR). The activation of this pathway likely is important in health and disease as many genetic diseases result from defective folding of mutant proteins. In addition, protein aggregation is an initiating event for many neurodegenerative diseases, such as Alzheimer’s disease. Our recent studies also suggest that the UPR is important as a central regulator of glucose metabolism as disruptions in this pathway may lead to pancreas dysfunction and hyperglycemia. Understanding the molecular basis for this cellular response should provide avenues to intervene in disease states.
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Kaufman, R.J. et al. (2001). The Cellular Response to Unfolded Proteins in the Endoplasmic Reticulum. In: Merten, OW., et al. Recombinant Protein Production with Prokaryotic and Eukaryotic Cells. A Comparative View on Host Physiology. Springer, Dordrecht. https://doi.org/10.1007/978-94-015-9749-4_2
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DOI: https://doi.org/10.1007/978-94-015-9749-4_2
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