Systems Biology of Recombinant 2G12 and 353/11 mAb Production in CHO-K1 Cell Lines at Phosphoproteome Level

<b>Background</b>: Chinese hamster ovary (CHO) cells are extensively used in the pharmaceutical industry for producing complex proteins, primarily because of their ability to perform human-like post-translational modifications. However, the efficiency of high-quality protein production c...

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Bibliographic Details
Main Authors: Eldi Sulaj, Felix L. Sandell, Linda Schwaigerlehner, Gorji Marzban, Juliane C. Dohm, Renate Kunert
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Proteomes
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Online Access:https://www.mdpi.com/2227-7382/13/1/9
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Summary:<b>Background</b>: Chinese hamster ovary (CHO) cells are extensively used in the pharmaceutical industry for producing complex proteins, primarily because of their ability to perform human-like post-translational modifications. However, the efficiency of high-quality protein production can vary significantly for monoclonal antibody-producing cell lines, within the CHO host cell lines or by extrinsic factors. <b>Methods</b>: To investigate the complex cellular mechanisms underlying this variability, a phosphoproteomics analysis was performed using label-free quantitative liquid chromatography after a phosphopeptide enrichment of recombinant CHO cells producing two different antibodies and a tunicamycin treatment experiment. Using MaxQuant and Perseus for data analysis, we identified 2109 proteins and quantified 4059 phosphosites. <b>Results</b>: Significant phosphorylation dynamics were observed in nuclear proteins of cells producing the difficult-to-produce 2G12 mAb. It suggests that the expression of 2G12 regulates nuclear pathways based on increases and decreases in phosphorylation abundance. Furthermore, a substantial number of changes in the phosphorylation pattern related to tunicamycin treatment have been detected. TM treatment affects, among other phosphoproteins, the eukaryotic elongation factor 2 kinase (Eef2k). <b>Conclusions</b>: The alterations in the phosphorylation landscape of key proteins involved in cellular processes highlight the mechanisms behind stress-induced cellular responses.
ISSN:2227-7382