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Title: Regulation of XBP-1 signaling during transient and stable recombinant protein production in CHO cells
Authors: Ku, S.C.Y.
Toh, P.C.
Lee, Y.Y.
Chusainow, J.
Yap, M.G.S. 
Chao, S.-H.
Keywords: CHO
Recombinant protein production
Issue Date: Mar-2010
Citation: Ku, S.C.Y., Toh, P.C., Lee, Y.Y., Chusainow, J., Yap, M.G.S., Chao, S.-H. (2010-03). Regulation of XBP-1 signaling during transient and stable recombinant protein production in CHO cells. Biotechnology Progress 26 (2) : 517-526. ScholarBank@NUS Repository.
Abstract: X-box binding protein 1 (XBP-1) is a key regulator of cellular unfolded protein response (UPR). The spliced isoform of XBP-1, XBP-1S, is a transcription activator, which is expressed only when UPR is induced. However, the impact of recombinant protein production on the regulation of XBP-1 signaling in CHO cells is not well understood. In this report, we cloned the Chinese hamster XBP-1 homolog to aid the investigation of the interplay between protein productivity, culture conditions, and endogenous XBP-1 signaling in CHO cells. Interestingly, expression of XBP-1S is detected in the non-producing and unstressed CHO-K1 cells. Transient expression of recombinant erythropoietin reveals a positive correlation between XBP-1 mRNA abundance and protein production level. However, such a correlation is not observed in batch cultivation of stable producing cell lines. The increased XBP-1 splicing is detected in late-phase cultures, suggesting that induction of XBP-1S may be a result of nutrient limitations or other environmental stresses rather than that of increased intracellular accumulation of recombinant proteins. Our data suggest that XBP-1 is a key determinant for the secretory capacity of CHO cells. Understanding its dynamic regulation hence provides a rational basis for cellular engineering strategies to improve recombinant protein secretion. © 2009 American Institute of Chemical Engineers Biotechnol.
Source Title: Biotechnology Progress
ISSN: 87567938
Appears in Collections:Staff Publications

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