Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-6-2
pubmed:abstractText
To improve the production of recombinant human antithrombin III (AT-III) in Chinese hamster ovary (CHO) cells, the genes encoding transcription factors, ATF4 (activating transcription factor 4) and XBP-1s (the spliced form of X-box binding protein 1), which were involved in the mammalian unfolded protein response (UPR), were cloned from CHO-K1 cells. Overexpression of ATF4 significantly enhanced the production of recombinant AT-III in CHO 13D-35D cells. The specific rate of AT-III production in the ATF4-overexpressed CHO 13D-35D cells reached approximately 23 pg/cell/day. After 144 h of incubation, the AT-III concentration in the culture supernatant was twofold greater compared to that observed with parental CHO 13D-35D cells. In contrast, ectopic expression of XBP-1s failed to enhance the production of recombinant AT-III in CHO 13D-35D cells. RT-PCR analysis revealed that high levels of XBP-1s mRNA were present in the CHO cells, regardless of ectopic expression of XBP-1s. Our results indicate that overexpression of the UPR transcription factor ATF4 is a promising means for improving the production of secreted protein pharmaceuticals in CHO cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1097-0290
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
100
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
317-24
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Improved production of recombinant human antithrombin III in Chinese hamster ovary cells by ATF4 overexpression.
pubmed:affiliation
Advanced Medical Protein Research Laboratory, Mitsubishi Tanabe Pharma Corporation, 2-25-1 Shodai-Ohtani, Hirakata, Osaka 573-1153, Japan. ohya.tomoshi@md.mt-pharma.co.jp
pubmed:publicationType
Journal Article