Regulation of XBP-1 signaling during transient and stable recombinant protein production in CHO cells

Biotechnology Progress
Sebastian Chih Yuan KuSheng-Hao Chao

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 regula...Continue Reading

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Citations

Oct 12, 2012·Applied Microbiology and Biotechnology·M Butler, A Meneses-Acosta
Sep 8, 2010·Nucleic Acids Research·Qiao Jing LewSheng-Hao Chao
Apr 16, 2010·Biotechnology and Applied Biochemistry·Yiping LimMiranda G S Yap

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