title: Improved antibody production in Chinese hamster ovary cells by ATF4 overexpression.
abstract: To improve antibody production in Chinese hamster ovary (CHO) cells, the humanized antibody-producing CHO DP-12-SF cell line was transfected with the gene encoding activating transcription factor 4 (ATF4), a central factor in the unfolded protein response. Overexpression of ATF4 significantly enhanced the production of antibody in the CHO DP-12-SF cell line. The specific IgG production rate of in the ATF4-overexpressing CHO-ATF4-16 cells was approximately 2.4 times that of the parental host cell line. Clone CHO-ATF4-16 did not show any change in growth rate compared with the parental cells or mock-transfected CHO-DP12-SF cells. The expression levels of mRNAs encoding both the antibody heavy and light chains in the CHO-ATF4-16 clone were analyzed. This analysis showed that ATF4 overexpression improved the total production and specific production rate of antibody without affecting the mRNA transcription level. These results indicate that ATF4 overexpression is a promising method for improving recombinant IgG production in CHO cells.
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Ahmad M
authors.initials: AM
authors.lastname: Haredy
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Nishizawa
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Honda
authors.forename: Tomoshi
authors.initials: T
authors.lastname: Ohya
authors.forename: Hisao
authors.initials: H
authors.lastname: Ohtake
authors.forename: Takeshi
authors.initials: T
authors.lastname: Omasa
references.citation: Appl Microbiol Biotechnol. 2010 Jan;85(3):535-42
references.pmid: 19652963
references.citation: Biotechnol Bioeng. 2004 Jan 20;85(2):115-21
references.pmid: 14704993
references.citation: Biotechnol Bioeng. 2007 Oct 15;98(3):611-5
references.pmid: 17421043
references.citation: J Biotechnol. 2004 Sep 30;113(1-3):171-82
references.pmid: 15380655
references.citation: Protein Expr Purif. 1995 Aug;6(4):537-45
references.pmid: 8527941
references.citation: Biotechnol Prog. 1997 Jan-Feb;13(1):96-104
references.pmid: 9041711
references.citation: Metab Eng. 2006 May;8(3):264-72
references.pmid: 16635796
references.citation: Mol Cell. 2009 Jun 12;34(5):569-79
references.pmid: 19524537
references.citation: FEMS Yeast Res. 2012 Aug;12(5):491-510
references.pmid: 22533807
references.citation: Biotechnol Bioeng. 2008 Jan 1;99(1):155-64
references.pmid: 17614336
references.citation: Appl Microbiol Biotechnol. 2013 Mar;97(6):2531-9
references.pmid: 22926643
references.citation: Biotechnol Bioeng. 2008 Jun 1;100(2):317-24
references.pmid: 18078289
references.citation: J Biosci Bioeng. 2010 May;109(5):504-11
references.pmid: 20347775
references.citation: Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):962-6
references.pmid: 1736312
references.citation: Adv Exp Med Biol. 2007;594:37-46
references.pmid: 17205673
references.citation: Trends Biochem Sci. 2010 Apr;35(4):189-98
references.pmid: 20022755
references.citation: Curr Pharm Biotechnol. 2010 Apr;11(3):233-40
references.pmid: 20210750
references.citation: Metab Eng. 2014 Jan;21:91-102
references.pmid: 23380542
references.citation: Biotechnol Bioeng. 2013 Apr;110(4):1164-73
references.pmid: 23124363
references.citation: Am J Physiol Endocrinol Metab. 2007 Jun;292(6):E1543-54
references.pmid: 17264231
references.citation: J Biosci Bioeng. 2008 Dec;106(6):568-73
references.pmid: 19134553
references.citation: Appl Microbiol Biotechnol. 2013 Jul;97(13):5731-41
references.pmid: 23615744
references.citation: Biochem J. 2008 Mar 15;410(3):485-93
references.pmid: 18052927
references.citation: J Cell Biol. 2004 Feb 2;164(3):341-6
references.pmid: 14757749
references.citation: Appl Microbiol Biotechnol. 2012 Apr;94(1):69-80
references.pmid: 22205442
references.citation: Mol Cell. 2003 Mar;11(3):619-33
references.pmid: 12667446
references.citation: Nat Biotechnol. 2004 Nov;22(11):1393-8
references.pmid: 15529164
references.citation: J Exp Med. 2008 May 12;205(5):1227-42
references.pmid: 18458112
references.citation: Biotechnol Bioeng. 2010 Aug 15;106(6):938-51
references.pmid: 20589672
references.citation: Biotechnol Prog. 2000 Sep-Oct;16(5):710-5
references.pmid: 11027161
references.citation: J Biosci Bioeng. 2002;94(6):600-5
references.pmid: 16233356
references.citation: J Immunother. 2008 Oct;31(8):752-61
references.pmid: 18779744
references.citation: Appl Microbiol Biotechnol. 2012 Nov;96(4):885-94
references.pmid: 23053101
references.citation: Curr Opin Biotechnol. 2006 Aug;17(4):381-6
references.pmid: 16806893
references.citation: Biotechnol Bioeng. 1997 Mar 20;53(6):547-59
references.pmid: 18634055
references.citation: Antioxid Redox Signal. 2009 Sep;11(9):2317-31
references.pmid: 19243234
references.citation: Nat Immunol. 2005 Jan;6(1):23-9
references.pmid: 15611778
references.citation: Annu Rev Cell Dev Biol. 2002;18:575-99
references.pmid: 12142265
references.citation: Cytotechnology. 2008 Jul;57(3):207-31
references.pmid: 19003179
references.citation: MAbs. 2011 Nov-Dec;3(6):568-76
references.pmid: 22123061
references.citation: Biotechnol Prog. 2010 Sep-Oct;26(5):1400-10
references.pmid: 20945494