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Uncoupling of cell growth and proliferation results in enhancement of productivity in p21 CIP1 ‐arrested CHO cells
Author(s) -
Bi JingXiu,
Shuttleworth John,
AlRubeai Mohamed
Publication year - 2004
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.20025
Subject(s) - cell growth , chinese hamster ovary cell , microbiology and biotechnology , productivity , cell culture , chemistry , biology , biochemistry , genetics , economics , macroeconomics
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. © 2004 Wiley Periodicals, Inc.