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Enhanced metabolism...
Enhanced metabolism and negative regulation of ER stress support higher erythropoietin production in HEK293 cells
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- Saghaleyni, Rasool, 1987 (author)
- Chalmers tekniska högskola,Chalmers University of Technology,Chalmers Univ Technol, Dept Biol & Biol Engn, S-41296 Gothenburg, Sweden.
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- Malm, Magdalena, 1983- (author)
- KTH,Proteinteknologi,Kungliga Tekniska Högskolan (KTH),Royal Institute of Technology (KTH)
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- Moruzzi, Noah (author)
- Karolinska Institutet
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- Zrimec, Jan, 1981 (author)
- Chalmers tekniska högskola,Chalmers University of Technology,Chalmers Univ Technol, Dept Biol & Biol Engn, S-41296 Gothenburg, Sweden.
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- Razavi, Ronia, 1979- (author)
- KTH,Proteinteknologi,Kungliga Tekniska Högskolan (KTH),Royal Institute of Technology (KTH)
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- Wistbacka, Num (author)
- KTH,Proteinteknologi,Kungliga Tekniska Högskolan (KTH),Royal Institute of Technology (KTH)
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- Thorell, Hannes, 1995- (author)
- KTH,Proteinteknologi,Kungliga Tekniska Högskolan (KTH),Royal Institute of Technology (KTH)
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- Pintar, Anton, 1995- (author)
- KTH,Proteinteknologi,Kungliga Tekniska Högskolan (KTH),Royal Institute of Technology (KTH)
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- Hober, Andreas, 1992- (author)
- KTH,Science for Life Laboratory, SciLifeLab,Systembiologi,Kungliga Tekniska Högskolan (KTH),Royal Institute of Technology (KTH)
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- Edfors, Fredrik, 1988- (author)
- KTH,Science for Life Laboratory, SciLifeLab,Systembiologi,Kungliga Tekniska Högskolan (KTH),Royal Institute of Technology (KTH)
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- Chotteau, Véronique, Docent, 1963- (author)
- KTH,Industriell bioteknologi,Kungliga Tekniska Högskolan (KTH),Royal Institute of Technology (KTH)
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- Berggren, Per Olof (author)
- Karolinska Institutet
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- Grassi, Luigi (author)
- AstraZeneca AB,AstraZeneca, BioPharmaceut R&D, BioPharmaceut Dev, Cell Culture & Fermentat Sci, Cambridge, England.
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- Zelezniak, Aleksej, 1984 (author)
- Chalmers tekniska högskola,Chalmers University of Technology,Chalmers Univ Technol, Dept Biol & Biol Engn, S-41296 Gothenburg, Sweden.
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- Svensson, Thomas, 1963 (author)
- Chalmers tekniska högskola,Chalmers University of Technology,Chalmers Univ Technol, Dept Biol & Biol Engn, S-41296 Gothenburg, Sweden.;Chalmers Univ Technol, Dept Biol & Biol Engn, Sci Life Lab, Natl Bioinformat Infrastruct Sweden, Kemivagen 10, S-41258 Gothenburg, Sweden.
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- Hatton, Diane (author)
- AstraZeneca AB,AstraZeneca, BioPharmaceut R&D, BioPharmaceut Dev, Cell Culture & Fermentat Sci, Cambridge, England.
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- Nielsen, Jens B, 1962 (author)
- Chalmers tekniska högskola,Chalmers University of Technology,Danmarks Tekniske Universitet,Technical University of Denmark,Chalmers Univ Technol, Dept Biol & Biol Engn, S-41296 Gothenburg, Sweden.;Tech Univ Denmark, Novo Nordisk Fdn Ctr Biosustainabil, DK-2800 Lyngby, Denmark.
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- Robinson, Jonathan, 1986 (author)
- Chalmers tekniska högskola,Chalmers University of Technology,Chalmers Univ Technol, Dept Biol & Biol Engn, S-41296 Gothenburg, Sweden.;Chalmers Univ Technol, Dept Biol & Biol Engn, Sci Life Lab, Natl Bioinformat Infrastruct Sweden, Kemivagen 10, S-41258 Gothenburg, Sweden.
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- Rockberg, Johan (author)
- KTH,Proteinteknologi,Kungliga Tekniska Högskolan (KTH),Royal Institute of Technology (KTH)
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Chalmers tekniska högskola Chalmers Univ Technol, Dept Biol & Biol Engn, S-41296 Gothenburg, Sweden (creator_code:org_t)
- Elsevier BV, 2022
- 2022
- English.
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 39:11
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https://doi.org/10.1...
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Abstract
Subject headings
Close
- Recombinant protein production can cause severe stress on cellular metabolism, resulting in limited titer and product quality. To investigate cellular and metabolic characteristics associated with these limitations, we compare HEK293 clones producing either erythropoietin (EPO) (secretory) or GFP (non-secretory) protein at different rates. Transcriptomic and functional analyses indicate significantly higher metabolism and oxidative phosphorylation in EPO producers compared with parental and GFP cells. In addition, ribosomal genes exhibit specific expression patterns depending on the recombinant protein and the production rate. In a clone displaying a dramatically increased EPO secretion, we detect higher gene expression related to negative regulation of endoplasmic reticulum (ER) stress, including upregulation of ATF6B, which aids EPO production in a subset of clones by overexpression or small interfering RNA (siRNA) knockdown. Our results offer potential target pathways and genes for further development of the secretory power in mammalian cell factories.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Mikrobiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Microbiology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- GFP
- HEK293
- ATF6B
- protein production
- CP: Molecular biology
- erythropoietin
- ribosome heterogeneity
- CP: Cell biology
- secretory pathways
- Cell engineering
Publication and Content Type
- art (subject category)
- ref (subject category)
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Saghaleyni, Raso ...
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Malm, Magdalena, ...
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Moruzzi, Noah
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Zrimec, Jan, 198 ...
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Razavi, Ronia, 1 ...
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Wistbacka, Num
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Thorell, Hannes, ...
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Pintar, Anton, 1 ...
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Hober, Andreas, ...
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Edfors, Fredrik, ...
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Chotteau, Véroni ...
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Berggren, Per Ol ...
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Grassi, Luigi
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Zelezniak, Aleks ...
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Svensson, Thomas ...
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Hatton, Diane
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Nielsen, Jens B, ...
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Robinson, Jonath ...
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Rockberg, Johan
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Microbiology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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and Medical Biotechn ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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- Articles in the publication
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Cell Reports
- By the university
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Chalmers University of Technology
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Royal Institute of Technology
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Karolinska Institutet