An 'omics approach towards CHO cell engineering

2013 ◽  
Vol 110 (5) ◽  
pp. 1255-1271 ◽  
Author(s):  
Payel Datta ◽  
Robert J. Linhardt ◽  
Susan T. Sharfstein
Keyword(s):  
2020 ◽  
Vol 9 (7) ◽  
pp. 1572-1580
Author(s):  
Youngsik Lee ◽  
Jin Myeong Kwak ◽  
Jae Seong Lee
Keyword(s):  

2020 ◽  
Vol 219 (7) ◽  
Author(s):  
Danming Tang ◽  
Wendy Sandoval ◽  
Cynthia Lam ◽  
Benjamin Haley ◽  
Peter Liu ◽  
...  

Accumulation of unfolded antibody chains in the ER triggers ER stress that may lead to reduced productivity in therapeutic antibody manufacturing processes. We identified UBR4 and UBR5 as ubiquitin E3 ligases involved in HC ER-associated degradation. Knockdown of UBR4 and UBR5 resulted in intracellular accumulation, enhanced secretion, and reduced ubiquitination of HC. In concert with these E3 ligases, PDIA3 was shown to cleave ubiquitinated HC molecules to accelerate HC dislocation. Interestingly, UBR5, and to a lesser degree UBR4, were down-regulated as cellular demand for antibody expression increased in CHO cells during the production phase, or in plasma B cells. Reducing UBR4/UBR5 expression before the production phase increased antibody productivity in CHO cells, possibly by redirecting antibody molecules from degradation to secretion. Altogether we have characterized a novel proteolysis/proteasome-dependent pathway involved in degradation of unfolded antibody HC. Proteins characterized in this pathway may be novel targets for CHO cell engineering.


Author(s):  
Tatiana Dovgan ◽  
Vahid Golghalyani ◽  
Fabio Zurlo ◽  
Diane Hatton ◽  
Viv Lindo ◽  
...  

2014 ◽  
Vol 21 ◽  
pp. 91-102 ◽  
Author(s):  
Valérie Le Fourn ◽  
Pierre-Alain Girod ◽  
Montse Buceta ◽  
Alexandre Regamey ◽  
Nicolas Mermod

2015 ◽  
Vol 33 (8) ◽  
pp. 1878-1896 ◽  
Author(s):  
Simon Fischer ◽  
René Handrick ◽  
Kerstin Otte

2012 ◽  
Vol 158 (1-2) ◽  
pp. 24-33 ◽  
Author(s):  
Ryan P. Nolan ◽  
Kyongbum Lee

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