Skip to main content

Functional proteomic analysis of GS-NS0 murine myeloma cell lines with varying recombinant monoclonal antibody production rate

Dinnis, Diane M., Stansfield, Scott H., Schlatter, Stefan, Smales, Christopher Mark, Alete, Daniel E., Birch, John R., Racher, Andrew J., Marshal, Carol T., Nielsen, Lars K., James, David C. and others. (2006) Functional proteomic analysis of GS-NS0 murine myeloma cell lines with varying recombinant monoclonal antibody production rate. Biotechnology and Bioengineering, 94 (5). pp. 830-841. ISSN 0006-3592. (doi:10.1002/bit.20899) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:6226)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided.
Official URL:
http://dx.doi.org/10.1002/bit.20899

Abstract

We previously compared changes in individual protein abundance between the proteomes of GS-NSO cell lines with varying rates of cell-specific recombinant monoclonal antibody production (qMab). Here we extend analyses of our proteomic clataset to statistically determine if particular cell lines have distinct functional capabilities that facilitate production of secreted recombinant Mab. We categorized 79 proteins identified by mass spectrometry according to their biological function or location in the cell and statistically compared the relative abundance of proteins in each category between GS-NSO cell lines with varying qMab. We found that the relative abundance of proteins in ER chaperone, non-ER chaperone, cytoskeletal, cell signaling, metabolic, and mitochondrial categories were significantly increased with qMab. As the GS-NSO cell line with highest qMab also had an increased intracellular abundance of unassembled Mab heavy chain (HC), we tested the hypothesis that the increased ER chaperone content was caused by induction of an unfolded protein response (UPR) signaling pathway. Immunoblot analyses revealed that spliced X-box binding protein 1 (XBP1), a marker for UPR induction, was not detectable in the GS-NSO cells with elevated qMab, although it was induced by chemical inhibitors of protein folding. These data suggest that qMab is functionally related to the abundance of specific categories of proteins that together facilitate recombinant protein production. We infer that individual cells within parental populations are more functionally equipped for high-level recombinant protein production than others and that this bias could be used to select cells that are more likely to achieve high qMab.

Item Type: Article
DOI/Identification number: 10.1002/bit.20899
Uncontrolled keywords: proteomics; recombinant monoclonal antibody; cell-specific production; murine myeloma; unfolded protein response
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Mark Smales
Date Deposited: 03 Sep 2008 07:21 UTC
Last Modified: 16 Nov 2021 09:44 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/6226 (The current URI for this page, for reference purposes)

University of Kent Author Information

Smales, Christopher Mark.

Creator's ORCID: https://orcid.org/0000-0002-2762-4724
CReDIT Contributor Roles:
  • Depositors only (login required):

Total unique views for this document in KAR since July 2020. For more details click on the image.