The Role of Endoplasmic Reticulum Stress on Reducing Recombinant Protein Production in Mammalian Cells
Therapeutic recombinant protein production relies on industrial scale culture of mammalian cells to produce active proteins in quantities sufficient for clinical use. The combination of stresses from industrial cell culture environment and recombinant protein production can overwhelm the protein syn...
| Veröffentlicht in: | Biochemical engineering journal. - 1998. - 210(2024) vom: 26. Sept. |
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| Format: | Online-Aufsatz |
| Sprache: | English |
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2024
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| Zugriff auf das übergeordnete Werk: | Biochemical engineering journal |
| Schlagworte: | Journal Article DNA Damage Response Endoplasmic reticulum stress Industrial Cell Culture Protein Production Secretion |
| Zusammenfassung: | Therapeutic recombinant protein production relies on industrial scale culture of mammalian cells to produce active proteins in quantities sufficient for clinical use. The combination of stresses from industrial cell culture environment and recombinant protein production can overwhelm the protein synthesis machinery in the endoplasmic reticulum (ER). This leads to a buildup of improperly folded proteins which induces ER stress. Cells respond to ER stress by activating the Unfolded Protein Response (UPR). To restore proteostasis, ER sensor proteins reduce global protein synthesis and increase chaperone protein synthesis, and if that is insufficient the proteins are degraded. If proteostasis is still not restored, apoptosis is initiated. Increasing evidence suggests crosstalk between ER proteostasis and DNA damage repair (DDR) pathways. External factors (e.g., metabolites) from the cellular environment as well as internal factors (e.g., transgene copy number) can impact genome stability. Failure to maintain genome integrity reduces cell viability and in turn protein production. This review focuses on the association between ER stress and processes that affect protein production and secretion. The processes mediated by ER stress, including inhibition of global protein translation, chaperone protein production, degradation of misfolded proteins, DNA repair, and protein secretion, impact recombinant protein production. Recombinant protein production can be reduced by ER stress through increased autophagy and protein degradation, reduced protein secretion, and reduced DDR response |
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| Beschreibung: | Date Revised 04.09.2024 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
| ISSN: | 1369-703X |
| DOI: | 10.1016/j.bej.2024.109434 |