Engineering of chaperone systems and of the unfolded protein response |
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Authors: | Saeed U Khan Martin Schröder |
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Institution: | (1) School of Biological and Biomedical Sciences, Durham University, South Road, Durham, DH1 3LE, UK |
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Abstract: | Production of recombinant proteins in mammalian cells is a successful technology that delivers protein pharmaceuticals for
therapies and for diagnosis of human disorders. Cost effective production of protein biopharmaceuticals requires extensive
optimization through cell and fermentation process engineering at the upstream and chemical engineering of purification processes
at the downstream side of the production process. The majority of protein pharmaceuticals are secreted proteins. Accumulating
evidence suggests that the folding and processing of these proteins in the endoplasmic reticulum (ER) is a general rate- and
yield limiting step for their production. We will summarize our knowledge of protein folding in the ER and of signal transduction
pathways activated by accumulation of unfolded proteins in the ER, collectively called the unfolded protein response (UPR).
On the basis of this knowledge we will evaluate engineering approaches to increase cell specific productivities through engineering
of the ER-resident protein folding machinery and of the UPR. |
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Keywords: | Endoplasmic reticulum associated protein degradation Heterologous protein production Molecular chaperone Protein folding Unfolded protein response |
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