ArticleThe Biochemical journal2016
mTORC1 signalling and eIF4E/4E-BP1 translation initiation factor stoichiometry influence recombinant protein productivity from GS-CHOK1 cells.
Article in The Biochemical journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 54 citations in OpenAlex.
- Using transcription and translation regulators to improve recombinant protein expression in CHO cells.Acta biochimica et biophysica Sinica · 2025Article
- Article
- CRISPR-Cas9 Mediated Stable Expression of Exogenous Proteins in the CHO Cell Line through Site-Specific Integration.International journal of molecular sciences · 2023Article
- Amino acid transporter SLC38A5 is a tumor promoter and a novel therapeutic target for pancreatic cancer.Scientific reports · 2023Article
- Cell factory engineering: Challenges and opportunities for synthetic biology applications.Biotechnology and bioengineering · 2023Review
- Autophagy-related gene and protein expressions during blastocyst development.Journal of assisted reproduction and genetics · 2023Article
- Enhancing productivity of Chinese hamster ovary (CHO) cells: synergistic strategies combining low-temperature culture and mTORC1 signaling engineering.Frontiers in bioengineering and biotechnology · 2023Article
- Small-molecule High-throughput Screening Identifies an MEK Inhibitor PD198306 that Enhances Sorafenib Efficacy via MCL-1 and BIM in Hepatocellular Carcinoma Cells.Combinatorial chemistry & high throughput screening · 2023Article
- NADPH oxidase 4 inhibition is a complementary therapeutic strategy for spinal muscular atrophy.Frontiers in cellular neuroscience · 2023Article
- Overview of Research into mTOR Inhibitors.Molecules (Basel, Switzerland) · 2022Review
- Review
- mTORC1 induces eukaryotic translation initiation factor 4E interaction with TOS-S6 kinase 1 and its activation.Cell cycle (Georgetown, Tex.) · 2021Article
- Adaptive responses toProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Subversion of Host Innate Immunity byFrontiers in immunology · 2021Article
- Racially Disparate Expression of mTOR/ERK-1/2 Allied Proteins in Cancer.Frontiers in cell and developmental biology · 2021Review
- Driver mutations of the adenoma-carcinoma sequence govern the intestinal epithelial global translational capacity.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- SOX2 and p53 Expression Control Converges in PI3K/AKT Signaling with Versatile Implications for Stemness and Cancer.International journal of molecular sciences · 2020Review
- Phospho-inositide-dependent kinase 1 regulates signal dependent translation in megakaryocytes and platelets.Journal of thrombosis and haemostasis : JTH · 2020Article
- Engineered transient and stable overexpression of translation factors eIF3i and eIF3c in CHOK1 and HEK293 cells gives enhanced cell growth associated with increased c-Myc expression and increased recombinant protein synthesis.Metabolic engineering · 2020Article
- T cell metabolism in graft-versus-host disease.Blood science (Baltimore, Md.) · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Many protein-based biotherapeutics are produced in cultured Chinese hamster ovary (CHO) cell lines. Recent reports have demonstrated that translation of recombinant mRNAs and global control of the translation machinery via mammalian target of rapamycin (mTOR) signalling are important determinants of the amount and quality of recombinant protein such cells can produce. mTOR complex 1 (mTORC1) is a master regulator of cell growth/division, ribosome biogenesis and protein synthesis, but the relationship between mTORC1 signalling, cell growth and proliferation and recombinant protein yields from mammalian cells, and whether this master regulating signalling pathway can be manipulated to enhance cell biomass and recombinant protein production (rPP) are not well explored. We have investigated mTORC1 signalling and activity throughout batch culture of a panel of sister recombinant glutamine synthetase-CHO cell lines expressing different amounts of a model monoclonal IgG4, to evaluate the links between mTORC1 signalling and cell proliferation, autophagy, recombinant protein expression, global protein synthesis and mRNA translation initiation. We find that the expression of the mTORC1 substrate 4E-binding protein 1 (4E-BP1) fluctuates throughout the course of cell culture and, as expected, that the 4E-BP1 phosphorylation profiles change across the culture. Importantly, we find that the eIF4E/4E-BP1 stoichiometry positively correlates with cell productivity. Furthermore, eIF4E amounts appear to be co-regulated with 4E-BP1 amounts. This may reflect a sensing of either change at the mRNA level as opposed to the protein level or the fact that the phosphorylation status, as well as the amount of 4E-BP1 present, is important in the co-regulation of eIF4E and 4E-BP1.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.