Source:http://linkedlifedata.com/resource/pubmed/id/18078289
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2008-6-2
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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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ATF4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Activating Transcription Factor 4,
http://linkedlifedata.com/resource/pubmed/chemical/Antithrombin III,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/regulatory factor X transcription...
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1097-0290
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
100
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
317-24
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:18078289-Activating Transcription Factor 4,
pubmed-meshheading:18078289-Animals,
pubmed-meshheading:18078289-Antithrombin III,
pubmed-meshheading:18078289-CHO Cells,
pubmed-meshheading:18078289-Cricetinae,
pubmed-meshheading:18078289-Cricetulus,
pubmed-meshheading:18078289-DNA-Binding Proteins,
pubmed-meshheading:18078289-Genetic Enhancement,
pubmed-meshheading:18078289-Humans,
pubmed-meshheading:18078289-Nuclear Proteins,
pubmed-meshheading:18078289-Protein Engineering,
pubmed-meshheading:18078289-Recombinant Proteins,
pubmed-meshheading:18078289-Transcription Factors
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pubmed:year |
2008
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pubmed:articleTitle |
Improved production of recombinant human antithrombin III in Chinese hamster ovary cells by ATF4 overexpression.
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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
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pubmed:publicationType |
Journal Article
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