Abstract:
:In this study, we assessed the importance of cytoskeleton organization in the mammalian cells used to produce therapeutic proteins. Two cytoskeletal genes, Actin alpha cardiac muscle 1 (ACTC1) and a guanosine triphosphate GTPase-activating protein (TAGAP), were found to be upregulated in highly productive therapeutic protein-expressing Chinese hamster ovary (CHO) cells selected by the deprivation of vitamin B5. We report here that the overexpression of the ACTC1 protein was able to improve significantly recombinant therapeutic production, as well as to decrease the levels of toxic lactate metabolic by-products. ACTC1 overexpression was accompanied by altered as well as decreased polymerized actin, which was associated with high protein production by CHO cell cultured in suspension. We suggest that the depolymerization of actin and the possible modulation of integrin signaling, as well as changes in basal metabolism, may be driving the increase of protein secretion by CHO cells.
journal_name
Biotechnol Bioengjournal_title
Biotechnology and bioengineeringauthors
Pourcel L,Buron F,Arib G,Le Fourn V,Regamey A,Bodenmann I,Girod PA,Mermod Ndoi
10.1002/bit.27277subject
Has Abstractpub_date
2020-04-01 00:00:00pages
1117-1126issue
4eissn
0006-3592issn
1097-0290journal_volume
117pub_type
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