ATF6β-based fine-tuning of the unfolded protein response enhances therapeutic antibody productivity of Chinese hamster ovary cells

2017 ◽  
Vol 114 (6) ◽  
pp. 1310-1318 ◽  
Author(s):  
Lisa A. Pieper ◽  
Michaela Strotbek ◽  
Till Wenger ◽  
Monilola A. Olayioye ◽  
Angelika Hausser
Keyword(s):  
Unfolded Protein Response ◽  
Chinese Hamster Ovary ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Fine Tuning ◽  
Ovary Cells ◽  
Unfolded Protein ◽  
Antibody Productivity ◽  
The Unfolded Protein Response ◽  
Protein Response

The unfolded protein response in a dolichyl phosphate mannose-deficient Chinese hamster ovary cell line points out the key role of a demannosylation step in the quality-control mechanism of N-glycoproteins

2002 ◽  
Vol 362 (2) ◽  
pp. 491-498 ◽  
Author(s):  
François FOULQUIER ◽  
Anne HARDUIN-LEPERS ◽  
Sandrine DUVET ◽  
Ingrid MARCHAL ◽  
Anne Marie MIR ◽  
...  
Keyword(s):  
Quality Control ◽  
Control System ◽  
Unfolded Protein Response ◽  
Cell Line ◽  
Chinese Hamster Ovary ◽  
Chinese Hamster ◽  
Quality Control System ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

The CHO (Chinese hamster ovary) glycosylation mutant cell line, B3F7, transfers the truncated glycan Glc3Man5GlcNAc2 on to nascent proteins. After deglucosylation, the resulting Man5GlcNAc2 glycan is subjected to two reciprocal enzymic processes: the action of an endoplasmic-reticulum (ER) kifunensine-sensitive α1,2-mannosidase activity to yield a Man4GlcNAc2 glycan, and the reglucosylation involved in the quality-control system which ensures that only correctly folded glycoproteins leave the ER. We show that the recombinant secreted alkaline phosphatase (SeAP) produced in stably transfected B3F7 cells, is co-immunoprecipitated with the GRP78 (glucose-regulated protein 78), a protein marker of the unfolded protein response (UPR). The level of GRP78 transcription has been evaluated by reverse transcription-PCR (RT-PCR) and we demonstrate that B3F7 cells present a constitutively higher level of UPR in the absence of inductors, compared with Pro−5 cells. Interestingly, a decrease was observed in the UPR and an increase in SeAP secretion in the kifunensine-treated B3F7 cells. Altogether, these data highlight the relationships between the glycan structure, the quality control system and the UPR. Moreover, they support the idea that a specific demannosylation step is a key event of the glycoprotein quality control in B3F7 cells.

scholarly journals Biological insights into the expression of translation initiation factors from recombinant CHOK1SV cell lines and their relationship to enhanced productivity

2015 ◽  
Vol 472 (3) ◽  
pp. 261-273 ◽  
Author(s):  
Emma J. Mead ◽  
Rosalyn J. Masterton ◽  
Marc Feary ◽  
Olga Obrezanova ◽  
Lin Zhang ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Chinese Hamster Ovary ◽  
Closed Loop ◽  
Chinese Hamster Ovary Cells ◽  
Recombinant Antibody ◽  
Chinese Hamster ◽  
Ovary Cells ◽  
Initiation Factors ◽  
Translation Initiation Factors ◽  
Antibody Productivity

We show for translation initiation factors involved in formation of the closed loop mRNA, their expression is associated with recombinant antibody productivity in Chinese hamster ovary cells and maintaining these is important in determining the cells capacity for antibody productivity.

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