Influence of cytoskeleton organization on recombinant protein expression by CHO cells

被引：15

作者：

Pourcel, Lucille ^{[1
,3
]}

Buron, Flavien ^{[1
]}

Arib, Ghislaine ^{[2
]}

Le Fourn, Valerie ^{[2
]}

Regamey, Alexandre ^{[2
]}

Bodenmann, Iris ^{[2
]}

Girod, Pierre-Alain ^{[2
]}

Mermod, Nicolas ^{[1
]}

机构：

[1] Univ Lausanne, Inst Biotechnol, Dept Fundamental Microbiol, CH-1015 Lausanne, Switzerland

[2] Selexis SA, Geneva, Switzerland

[3] Swiss Inst Bioinformat, Swiss Prot, Geneva, Switzerland

来源：

BIOTECHNOLOGY AND BIOENGINEERING | 2020年 / 117卷 / 04期

关键词：

actin polymerization; CHO cells; cytoskeleton regulation; recombinant protein production; ACTIN CYTOSKELETON; ACTIVATION; LACTATE;

D O I：

10.1002/bit.27277

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

收藏

页码：1117 / 1126

页数：10

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