{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T16:49:09Z","timestamp":1789836549262,"version":"4.0.1"},"reference-count":76,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland Frontiers for the Future Award","doi-asserted-by":"publisher","award":["19\/FFP\/6759"],"award-info":[{"award-number":["19\/FFP\/6759"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science Foundation Ireland Infrastructure Award","award":["SFI 16\/RI\/3701"],"award-info":[{"award-number":["SFI 16\/RI\/3701"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Chinese hamster ovary (CHO) cells are widely utilised in the biopharmaceutical industry to produce therapeutic proteins. Understanding the mechanisms of endoplasmic reticulum (ER) stress and its interplay with protein degradation pathways remains pivotal for improving production efficiency and product quality. In this study, we investigated the proteomic responses of CHO-K1 (non-producer), CHO DP-12 (IgG-producer), and NISTCHO (IgG-producer) cell lines under ER stress induced by a combination of the proteasome inhibitor MG132 and the glycosylation inhibitor tunicamycin. Viability, cell growth, and IgG titre were measured after 24 h, 48 h, and 72 h of treatment and the 48 h timepoint was used for the comparative analysis of the proteomic data across the three cell lines. Proteasome inhibition with MG132 intensified ER stress and altered ER-associated protein degradation (ERAD). Combined tunicamycin + MG132 treatment was associated with cell line-specific proteomic changes: NISTCHO upregulated ER translocation and glycoprotein quality control proteins (SSR4, SEC24C, UGGT1), CHO DP-12 activated redox\/disulfide regulators (DNAJC10, CAPN1), while CHO-K1 showed broad proteome shifts, suggesting differences in baseline stress handling. These findings provide mechanistic insights into ER stress and protein quality control in CHO cells, offering a foundation for strategies to enhance cell line robustness and optimise biopharmaceutical production.<\/jats:p>","DOI":"10.3390\/biom16020277","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T12:07:06Z","timestamp":1770725226000},"page":"277","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Proteasome Inhibition Amplifies Endoplasmic Reticulum (ER) Stress Responses: Comparative Proteomics of Chinese Hamster Ovary Cell Lines"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0558-1577","authenticated-orcid":false,"given":"Christiana-Kondylo","family":"Sideri","sequence":"first","affiliation":[{"name":"Life Sciences Institute, Dublin City University, D09 K20V Dublin, Ireland"},{"name":"School of Biotechnology, Dublin City University, D09 K20V Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Ryan","sequence":"additional","affiliation":[{"name":"Life Sciences Institute, Dublin City University, D09 K20V Dublin, Ireland"},{"name":"School of Biotechnology, Dublin City University, D09 K20V Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5312-4961","authenticated-orcid":false,"given":"Michael","family":"Henry","sequence":"additional","affiliation":[{"name":"Life Sciences Institute, Dublin City University, D09 K20V Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3380-0499","authenticated-orcid":false,"given":"Esen","family":"Efeoglu","sequence":"additional","affiliation":[{"name":"Life Sciences Institute, Dublin City University, D09 K20V Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5306-310X","authenticated-orcid":false,"given":"Paula","family":"Meleady","sequence":"additional","affiliation":[{"name":"Life Sciences Institute, Dublin City University, D09 K20V Dublin, Ireland"},{"name":"School of Biotechnology, Dublin City University, D09 K20V Dublin, Ireland"},{"name":"SSPC Research Ireland Centre for Pharmaceuticals, V94 T9PX Limerick, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/d41573-024-00199-w","article-title":"Top product forecasts for 2025","volume":"24","author":"Verdin","year":"2025","journal-title":"Nat. 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