Cited by 96Viral Infectious Diseases and Gene Expression in InsectsEndoplasmic Reticulum Stress and DiseaseProtein purification and stability

Improved production of recombinant human antithrombin III in Chinese hamster ovary cells by ATF4 overexpression

Ohya, Tomoshi, Hayashi, Tetsuji, Kiyama, Eriko, Nishii, Hiroko, Miki, Hideo, Kobayashi, Kaoru, Honda, Kohsuke, Omasa, Takeshi +1 more·2008·Biotechnology and Bioengineering

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. Biotechnol. Bioeng. 2008;100: 317–324. © 2007 Wiley Periodicals, Inc.

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  • ATF4 has been overexpressed to restore translation and enhance levels of anti-thrombin III produced in CHO cells.

    “ATF4, another critical transcription factor in the UPR system, has been overexpressed to restore translation and enhance levels of anti-thrombin III produced in CHO cells (Ohya et al., 2008).”

    From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Ohya et al., 2008

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Authors
Ohya, T., Hayashi, T., Kiyama, E., Nishii, H., Miki, H., Kobayashi, K., Honda, K., Omasa, T., & Ohtake, H.
Affiliations
  • Tanabe Pharma Corporation (Japan) (JP)
  • The University of Osaka (JP)
Corresponding author
Ohya, Tomoshi
Venue
Biotechnology and Bioengineering
Publisher
Wiley
Published
2007-12-13
Volume
100
Issue
2
Pages
317-324
ISSN
  • 0006-3592 (ISSN-L)
  • 1097-0290
OpenAlex
W2102232272
Cited by
96
References
31
Citations by year
2026: 1 · 2025: 6 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 7 · 2018: 4 · 2017: 8 · 2016: 4 · 2015: 6 · 2014: 7 · 2013: 9 · 2012: 5
FWCI
2.77
Type
journal article
Language
en
Open access
closed
Locations
  • Biotechnology and Bioengineering (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
Keywords
ATF4, XBP1, unfolded protein response, CHO cells, transcription factor overexpression, therapeutic proteins
MeSH terms
Regulatory Factor X Transcription Factors, X-Box Binding Protein 1, Animals, Antithrombin III, Cricetulus, DNA-Binding Proteins, Cricetinae, Humans, Nuclear Proteins, Recombinant Proteins, Transcription Factors, Protein Engineering, CHO Cells, Genetic Enhancement, Activating Transcription Factor 4

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