Multiplexed Digital mRNA Expression Analysis Profiles System‐Wide Changes in mRNA Abundance and Responsiveness of UPR‐Specific Gene Expression Changes During Batch Culture of Recombinant Chinese Hamster Ovary Cells

Multiplexed Digital mRNA Expression Analysis Profiles System‐Wide Changes in mRNA Abundance and... IntroductionThe accumulation of abnormally folded proteins in the ER lumen, a cellular condition referred to as ER stress, activates the UPR to restore proteostasis. The UPR integrates information about the intensity and duration of the stimuli, engaging adaptive programs to reduce the unfolded protein load. This adaptive response involves the upregulation of several ER chaperones and foldases, inhibition of general protein translation, and increased phospholipid synthesis with subsequent ER membrane expansion. Additionally, degradation of abnormally folded proteins through the ER‐associated protein degradation (ERAD) pathway and autophagy is increased. Failure to overcome ER stress, however, engages the core apoptosis machinery. Cells in batch culture are exposed to a combination of stimuli that can activate the UPR, especially during late stages of cell culture. While recombinant protein (RP) expression may be an important stimulus, conditions such as nutrient depletion (i.e., glucose), osmotic stress, and oxidative stress have also been shown to trigger UPR. Several components of the UPR signaling pathway have been engineered in mammalian cells with the aim of increasing RP production. Specifically, these include a number of chaperones such as BIP, calnexin, and calreticulin, members of the PDI family and components of the UPR signaling pathway such as CHOP, http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Biotechnology Journal Wiley

Multiplexed Digital mRNA Expression Analysis Profiles System‐Wide Changes in mRNA Abundance and Responsiveness of UPR‐Specific Gene Expression Changes During Batch Culture of Recombinant Chinese Hamster Ovary Cells

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Publisher
Wiley
Copyright
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
ISSN
1860-6768
eISSN
1860-7314
D.O.I.
10.1002/biot.201700429
Publisher site
See Article on Publisher Site

Abstract

IntroductionThe accumulation of abnormally folded proteins in the ER lumen, a cellular condition referred to as ER stress, activates the UPR to restore proteostasis. The UPR integrates information about the intensity and duration of the stimuli, engaging adaptive programs to reduce the unfolded protein load. This adaptive response involves the upregulation of several ER chaperones and foldases, inhibition of general protein translation, and increased phospholipid synthesis with subsequent ER membrane expansion. Additionally, degradation of abnormally folded proteins through the ER‐associated protein degradation (ERAD) pathway and autophagy is increased. Failure to overcome ER stress, however, engages the core apoptosis machinery. Cells in batch culture are exposed to a combination of stimuli that can activate the UPR, especially during late stages of cell culture. While recombinant protein (RP) expression may be an important stimulus, conditions such as nutrient depletion (i.e., glucose), osmotic stress, and oxidative stress have also been shown to trigger UPR. Several components of the UPR signaling pathway have been engineered in mammalian cells with the aim of increasing RP production. Specifically, these include a number of chaperones such as BIP, calnexin, and calreticulin, members of the PDI family and components of the UPR signaling pathway such as CHOP,

Journal

Biotechnology JournalWiley

Published: Jan 1, 2018

Keywords: ; ; ; ;

References

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