論文 - 詳細
| RRC ID | 43202 |
|---|---|
| 著者 | Ohya T, Hayashi T, Kiyama E, Nishii H, Miki H, Kobayashi K, Honda K, Omasa T, Ohtake H. |
| タイトル | Improved production of recombinant human antithrombin III in Chinese hamster ovary cells by ATF4 overexpression. |
| ジャーナル | Biotechnol Bioeng |
| Abstract |
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. |
| 巻・号 | 100(2) |
| ページ | 317-24 |
| 公開日 | 2008-6-1 |
| DOI | 10.1002/bit.21758 |
| PMID | 18078289 |
| MeSH | Activating Transcription Factor 4 / genetics Activating Transcription Factor 4 / metabolism* Animals Antithrombin III / biosynthesis* Antithrombin III / genetics CHO Cells / metabolism* Cricetinae Cricetulus DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Genetic Enhancement / methods* Humans Nuclear Proteins / genetics Nuclear Proteins / metabolism* Protein Engineering / methods* Recombinant Proteins / biosynthesis Regulatory Factor X Transcription Factors Transcription Factors X-Box Binding Protein 1 |
| IF | 4.002 |
| 引用数 | 70 |
| WOS 分野 | BIOTECHNOLOGY & APPLIED MICROBIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | CHO-K1(RCB0285) |