Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/46432
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Type: Journal article
Title: Uncoupling of cell growth and proliferation results in enhancement of productivity in p21CIP1-arrested CHO cells
Author: Bi, J.
Shuttleworth, J.
Al-Rubeai, M.
Citation: Biotechnology and Bioengineering, 2004; 85(7):741-749
Publisher: John Wiley & Sons Inc
Issue Date: 2004
ISSN: 0006-3592
1097-0290
Abstract: Chinese hamster ovary cells have been engineered to inducibly over-express the p21(CIP1) cyclin-dependent kinase inhibitor, to achieve cell cycle arrest and increase cell productivity. In p21(CIP1)-arrested cells production of antibody from a stably integrated lgG4 gene, was enhanced approximately fourfold. The underlying physiological basis for enhanced productivity was investigated by measuring a range of cellular and metabolic parameters. Interestingly, the average cell volume of arrested cells was approximately fourfold greater than that of proliferating cells. This was accompanied by significant increases in mitochondrial mass, mitochondrial activity, and ribosomal protein S6 levels. Our results suggest that p21(CIP1)-induced cell cycle arrest uncouples cell growth from cell-cycle progression, and provides new insight into how improved productivity can be achieved in a cell line commonly used for large-scale production of pharmaceutical proteins.
Keywords: cyclin-dependent kinase; cell cycle arrest; growth control; metabolic engineering
Description: Copyright © 2005 Wiley Periodicals The definitive version may be found at www.wiley.com
RMID: 0020081601
DOI: 10.1002/bit.20025
Appears in Collections:Chemical Engineering publications

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