Transcriptional Profiling of Gene Expression Changes in a PACE-Transfected CHO DUKX Cell Line Secreting High Levels of rhBMP-2
详细信息 查看全文
- 作者：Padraig Doolan (1)
Mark Melville (2)
Patrick Gammell (1) (3)
Martin Sinacore (2)
Paula Meleady (1)
Kevin McCarthy (2)
Linda Francullo (2)
Mark Leonard (2)
Timothy Charlebois (2)
Martin Clynes (1) - 关键词：Bone morphogenic protein ; Paired basic amino acid cleaving enzyme ; Expression microarray ; Hierarchical clustering ; Pathway analysis ; Endoplasmic reticulum stress pathway
- 刊名：Molecular Biotechnology
- 出版年：2008
- 出版时间：July 2008
- 年：2008
- 卷：39
- 期：3
- 页码：187-199
- 全文大小：430KB
- 参考文献：1. Arden, N., & Betenbaugh, M. J. (2004). Life and death in mammalian cell culture: Strategies for apoptosis inhibition. / Trends in Biotechnology, 22, 174-80. CrossRef
2. Butler, M. (2005). Animal cell cultures: Recent achievements and perspectives in the production of biopharmaceuticals. / Applied Microbiology and Biotechnology, 68, 283-91. CrossRef
3. Furukawa, K., & Ohsuye, K. (1998). Effect of culture temperature on a recombinant CHO cell line producing a C-terminal alpha-amidating enzyme. / Cytotechnology, 26, 153-64. CrossRef
4. Furukawa, K., & Ohsuye, K. (1999). Enhancement of productivity of recombinant alpha-amidating enzyme by low temperature culture. / Cytotechnology, 31, 85-4. CrossRef
5. Ishaque, A., & Al-Rubeai, M. (2002). Role of vitamins in determining apoptosis and extent of suppression by bcl-2 during hybridoma cell culture. / Apoptosis, 7, 231-39. CrossRef
6. Keenan, J., Pearson, D., & Clynes, M. (2006). The role of recombinant proteins in the development of serum-free media. / Cytotechnology, 50, 49-6. CrossRef
7. Kretzmer, G. (2002). Industrial processes with animal cells. / Applied Microbiology and Biotechnology, 59, 135-42. CrossRef
8. Underhill, M. F., Coley, C., Birch, J. R., Findlay, A., Kallmeier, R., Proud, C. G., & James, D. C. (2003). Engineering mRNA translation initiation to enhance transient gene expression in chinese hamster ovary cells. / Biotechnology Progress, 19, 121-29. CrossRef
9. Johansen, T. E., O’Hare, M. M., Wulff, B. S., & Schwartz, T. W. (1991). CHO cells synthesize amidated neuropeptide Y from a C-peptide deleted form of the precursor. / Endocrinology, 129, 553-55. CrossRef
10. Prati, E. G., Matasci, M., Suter, T. B., Dinter, A., Sburlati, A. R., & Bailey, J. E. (2002). Engineering of coordinated up- and down-regulation of two glycosyltransferases of the O-glycosylation pathway in Chinese hamster ovary (CHO) cells. / Biotechnology and Bioengineering, 79, 580-85. CrossRef
11. Umana, P., Jean-Mairet, J., Moudry, R., Amstutz, H., & Bailey, J. E. (1999). Engineered glycoforms of an antineuroblastoma IgG1 with optimized antibody-dependent cellular cytotoxic activity. / Nature Biotechnology, 17, 176-80. CrossRef
12. Tigges, M., & Fussenegger, M. (2006). Xbp1-based engineering of secretory capacity enhances the productivity of Chinese hamster ovary cells. / Metabolic Engineering, 8, 264-72. CrossRef
13. Wang, E. A., Rosen, V., D’Alessandro, J. S., Bauduy, M., Cordes, P., Harada, T., Israel, D. I., Hewick, R. M., Kerns, K. M., & LaPan, P. (1990). Recombinant human bone morphogenetic protein induces bone formation. / Proceedings of the National Academy of Sciences of the United States of America, 87, 2220-224. CrossRef
14. Ayoubi, T. A., Meulemans, S. M., Roebroek, A. J., & Van de Ven, W. J. (1996). Production of recombinant proteins in Chinese hamster ovary cells overexpressing the subtilisin-like proprotein converting enzyme furin. / Molecular Biology Reports, 23, 87-5. CrossRef
15. Wasley, L. C., Rehemtulla, A., Bristol, J. A., & Kaufman, R. J. (1993). PACE/furin can process the vitamin K-dependent pro-factor IX precursor within the secretory pathway. / Journal of Biological Chemistry, 268, 8458-465.
16. Wong, M. J., Goldberger, G., Isenman, D. E., & Minta, J. O. (1995). Processing of human factor I in COS-1 cells co-transfected with factor I and paired basic amino acid cleaving enzyme (PACE) cDNA. / Molecular Immunology, 32, 379-87. CrossRef
17. Roe, S., Francullo, L. E., Paradis, T. M., Porter, T. J., Leonard, M. W., & Charlebois, T. S. (2004). Effects of posttranslational processing on rhBMP-2 cellular productivity and product quality. / Bioprocess International, 2, 32-3.
18. Baik, J. Y., Lee, M. S., An, S. R., Yoon, S. K., Joo, E. J., Kim, Y. H., Park, H. W., & Lee, G. M. (2006). Initial transcriptome and proteome analyses of low culture temperature-induced expression in CHO cells producing erythropoietin. / Biotechnology and Bioengineering, 93, 361-71. CrossRef
19. Wong, D. C. F., Wong, K. T. K., Lee, Y. Y., Morin, P. N., Heng, C. K., & Yap, M. G. S. (2006). Transcriptional profiling of apoptotic pathways in batch and fed-batch CHO cell cultures. / Biotechnology and Bioengineering, 94, 373-82. CrossRef
20. Wise, R. J., Barr, P. J., Wong, P. A., Kiefer, M. C., Brake, A. J., & Kaufman, R. J. (1990). Expression of a human proprotein processing enzyme: Correct cleavage of the von Willebrand factor precursor at a paired basic amino acid site. / Proceedings of the National Academy of Sciences of the United States of America, 87, 9378-382. CrossRef
21. Rehemtulla, A., & Kaufman, R. J. (1992). Preferred sequence requirements for cleavage of pro-von Willebrand factor by propeptide-processing enzymes. / Blood, 79, 2349-355.
22. Hill, A. A., Brown, E. L., Whitley, M. Z., Tucker-Kellogg, G., Hunter, C. P., & Slonim, D. K. (2001). Evaluation of normalization procedures for oligonucleotide array data based on spiked cRNA controls. / Genome Biology 2, 12, Research 0055.1-055.13.
23. Li, C., & Wong, W. H. (2001). Model-based analysis of oligonucleotide arrays: Expression index computation and outlier detection. / Proceedings of the National Academy of Sciences of the United States of America, 98, 31-6. CrossRef
24. Smales, C. M., Dinnis, D. M., Stansfield, S. H., Alete, D., Sage, E. A., Birch, J. R., Racher, A. J., Marshall, C. T., & James, D. C. (2004). Comparative proteomic analysis of GS-NS0 murine myeloma cell lines with varying recombinant monoclonal antibody production rate. / Biotechnology and Bioengineering, 88, 474-88. CrossRef
25. Bassi, D. E., Fu, J., Lopez de Cicco, R., & Klein-Szanto, A. J. (2005). Proprotein convertases: “master switches-in the regulation of tumor growth and progression. / Molecular Carcinogenesis, 44, 151-61. CrossRef
26. Thomas, G. (2002). Furin at the cutting edge: From protein traffic to embryogenesis and disease. / Nature Reviews: Molecular Cell Biology, 3, 753-66. CrossRef
27. Dubois, C. M., Blanchette, F., Laprise, M. H., Leduc, R., Grondin, F., & Seidah, N. G. (2001). Evidence that furin is an authentic transforming growth factor-beta1-converting enzyme. / American Journal of Pathology, 158, 305-16.
28. McMahon, S., Charbonneau, M., Grandmont, S., Richard, D. E., & Dubois, C. M. (2006). Transforming growth factor beta1 induces hypoxia-inducible factor-1 stabilization through selective inhibition of PHD2 expression. / Journal of Biological Chemistry, 281, 24171-4181. CrossRef
29. Blanchette, F., Day, R., Dong, W., Laprise, M. H., & Dubois, C. M. (1997). TGFbeta1 regulates gene expression of its own converting enzyme furin. / Journal of Clinical Investigation, 99, 1974-983. CrossRef
30. Anders, L., Mertins, P., Lammich, S., Murgia, M., Hartmann, D., Saftig, P., Haass, C., & Ullrich, A. (2006). Furin-, ADAM 10-, and gamma-secretase-mediated cleavage of a receptor tyrosine phosphatase and regulation of beta-catenin’s transcriptional activity. / Molecular and Cellular Biology, 26, 3917-934. CrossRef
31. Kaufman, R. J. (1999). Stress signaling from the lumen of the endoplasmic reticulum: Coordination of gene transcriptional and translational controls. / Genes & Development, 13, 1211-233. CrossRef
32. Kaufman, R. J., Scheuner, D., Schroder, M., Shen, X., Lee, K., Liu, C. Y., & Arnold, S. M. (2002). The unfolded protein response in nutrient sensing and differentiation. / Nature Reviews: Molecular Cell Biology, 3, 411-21. CrossRef
33. Mori, K. (2000). Tripartite management of unfolded proteins in the endoplasmic reticulum. / Cell, 101, 451-54. CrossRef
34. Dorner, A. J., Wasley, L. C., & Kaufman, R. J. (1992). Overexpression of GRP78 mitigates stress induction of glucose regulated proteins and blocks secretion of selective proteins in Chinese hamster ovary cells. / EMBO Journal, 11, 1563-571.
35. Katsumi, A., Senda, T., Yamashita, Y., Yamazaki, T., Hamaguchi, M., Kojima, T., Kobayashi, S., & Saito, H. (1996). Protein C Nagoya, an elongated mutant of protein C, is retained within the endoplasmic reticulum and is associated with GRP78 and GRP94. / Blood, 87, 4164-175.
36. Katsumi, A., Kojima, T., Senda, T., Yamazaki, T., Tsukamoto, H., Sugiura, I., Kobayashi, S., Miyata, T., Umeyama, H., & Saito, H. (1998). The carboxyl-terminal region of protein C is essential for its secretion. / Blood, 91, 3784-791.
37. Kuznetsov, G., Chen, L. B., & Nigam, S. K. (1997). Multiple molecular chaperones complex with misfolded large oligomeric glycoproteins in the endoplasmic reticulum. / Journal of Biological Chemistry, 272, 3057-063. CrossRef
38. Lin, H. Y., Masso-Welch, P., Di, Y. P., Cai, J. W., Shen, J. W., & Subjeck, J. R. (1993). The 170-kDa glucose-regulated stress protein is an endoplasmic reticulum protein that binds immunoglobulin. / Molecular Biology of the Cell, 4, 1109-119.
39. Little, E., & Lee, A. S. (1995). Generation of a mammalian cell line deficient in glucose-regulated protein stress induction through targeted ribozyme driven by a stress-inducible promoter. / Journal of Biological Chemistry, 270, 9526-534. CrossRef
40. Toman, P. D., Chisholm, G., McMullin, H., Giere, L. M., Olsen, D. R., Kovach, R. J., Leigh, S. D., Fong, B. E., Chang, R., Daniels, G. A., Berg, R. A., & Hitzeman, R. A. (2000). Production of recombinant human type I procollagen trimers using a four-gene expression system in the yeast / Saccharomyces cerevisiae. / Journal of Biological Chemistry, 275, 23303-3309. CrossRef
41. de Virgilio, M., Kitzmuller, C., Schwaiger, E., Klein, M., Kreibich, G., & Ivessa, N. E. (1999). Degradation of a short-lived glycoprotein from the lumen of the endoplasmic reticulum: The role of N-linked glycans and the unfolded protein response. / Molecular Biology of the Cell, 10, 4059-073.
42. Helenius, A. (1994). How N-linked oligosaccharides affect glycoprotein folding in the endoplasmic reticulum. / Molecular Biology of the Cell, 5, 253-65.
43. Yang, Y., Turner, R. S., & Gaut, J. R. (1998). The chaperone BiP/GRP78 binds to amyloid precursor protein and decreases Abeta40 and Abeta42 secretion. / Journal of Biological Chemistry, 273, 25552-5555. CrossRef
44. Kokame, K., Agarwala, K. L., Kato, H., & Miyata, T. (2000). Herp, a new ubiquitin-like membrane protein induced by endoplasmic reticulum stress. / Journal of Biological Chemistry, 275, 32846-2853. CrossRef
45. Chan, S. L., Fu, W., Zhang, P., Cheng, A., Lee, J., Kokame, K., & Mattson, M. P. (2004). Herp stabilizes neuronal Ca2+ homeostasis and mitochondrial function during endoplasmic reticulum stress. / Journal of Biological Chemistry, 279, 28733-8743. CrossRef
46. Mallet, W. G., & Maxfield, F. R. (1999). Chimeric forms of furin and TGN38 are transported with the plasma membrane in the trans-Golgi network via distinct endosomal pathways. / Journal of Cell Biology, 146, 345-59. CrossRef
47. Zhang, Y., & Allison, J. P. (1997). Interaction of CTLA-4 with AP50, a clathrin-coated pit adaptor protein. / Proceedings of the National Academy of Sciences of the United States of America, 94, 9273-278. CrossRef
48. Ohno, H., Fournier, M. C., Poy, G., & Bonifacino, J. S. (1996). Structural determinants of interaction of tyrosine-based sorting signals with the adaptor medium chains. / Journal of Biological Chemistry, 271, 29009-9015. CrossRef
49. Robinson, M. S. (1992). Adaptins. / Trends in Cell Biology, 2, 293-97. CrossRef
50. Jones, S. M., Crosby, J. R., Salamero, J., & Howell, K. E. (1993). A cytosolic complex of p62 and rab6 associates with TGN38/41 and is involved in budding of exocytic vesicles from the trans-Golgi network. / Journal of Cell Biology, 122, 775-88. CrossRef
51. Takahashi, S., Nakagawa, T., Banno, T., Watanabe, T., Murakami, K., & Nakayama, K. (1995). Localization of furin to the trans-Golgi network and recycling from the cell surface involves Ser and Tyr residues within the cytoplasmic domain. / Journal of Biological Chemistry, 270, 28397-8401. CrossRef
52. Nuoffer, C., & Balch, W. E. (1994). GTPases: Multifunctional molecular switches regulating vesicular traffic. / Annual Review of Biochemistry, 63, 949-90. CrossRef
53. Pfeffer, S. R. (1994). Rab GTPases: Master regulators of membrane trafficking. / Current Opinion in Cell Biology, 6, 522-26. CrossRef
54. Antony, C., Cibert, C., Geraud, G., Santa Maria, A., Maro, B., Mayau, V., & Goud, B. (1992). The small GTP-binding protein rab6p is distributed from medial Golgi to the trans-Golgi network as determined by a confocal microscopic approach. / Journal of Cell Science, 103(Pt 3), 785-96.
55. Deretic, D., & Papermaster, D. S. (1993). Rab6 is associated with a compartment that transports rhodopsin from the trans-Golgi to the site of rod outer segment disk formation in frog retinal photoreceptors. / Journal of Cell Science, 106(Pt 3), 803-13.
56. Martinez, O., Schmidt, A., Salamero, J., Hoflack, B., Roa, M., & Goud, B. (1994). The small GTP-binding protein rab6 functions in intra-Golgi transport. / Journal of Cell Biology, 127, 1575-588. CrossRef
57. Tixier-Vidal, A., Barret, A., Picart, R., Mayau, V., Vogt, D., Wiedenmann, B., & Goud, B. (1993). The small GTP-binding protein, Rab6p, is associated with both Golgi and post-Golgi synaptophysin-containing membranes during synaptogenesis of hypothalamic neurons in culture. / Journal of Cell Science, 105(Pt 4), 935-47.
58. Han, S. Y., Park, D. Y., Park, S. D., & Hong, S. H. (2000). Identification of Rab6 as an / N-ethylmaleimide-sensitive fusion protein-binding protein. / Biochemical Journal, 352(Pt 1), 165-73. CrossRef
59. DeBello, W. M., O’Connor, V, Dresbach, T., Whiteheart, S. W., Wang, S. S., Schweizer, F. E., Betz, H., Rothman, J. E., & Augustine, G. J. (1995). SNAP-mediated protein-protein interactions essential for neurotransmitter release. / Nature, 373, 626-30. CrossRef
60. Morgan, A., & Burgoyne, R. D. (1995). Is NSF a fusion protein? / Trends in Cell Biology, 5, 335-39. CrossRef
61. Haass, C., & De Strooper, B. (1999). The presenilins in Alzheimer’s disease—proteolysis holds the key. / Science, 286, 916-19. CrossRef
62. Sai, X., Kawamura, Y., Kokame, K., Yamaguchi, H., Shiraishi, H., Suzuki, R., Suzuki, T., Kawaichi, M., Miyata, T., Kitamura, T., De Strooper, B., Yanagisawa, K., & Komano, H. (2002). Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid beta-protein. / Journal of Biological Chemistry, 277, 12915-2920. CrossRef - 作者单位：Padraig Doolan (1)
Mark Melville (2)
Patrick Gammell (1) (3)
Martin Sinacore (2)
Paula Meleady (1)
Kevin McCarthy (2)
Linda Francullo (2)
Mark Leonard (2)
Timothy Charlebois (2)
Martin Clynes (1)
1. National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin, 9, Ireland
2. Wyeth Biopharma, 1 Burtt Rd., Andover, MA, 01810, USA
3. Wyeth Biotech, Grange Castle Business Park, Clondalkin, Dublin, 22, Ireland
文摘
Chinese hamster ovary (CHO) cells are widely used in the biopharmaceutical industry for the production of recombinant human proteins including complex polypeptides such as recombinant human bone morphogenic protein 2 (rhBMP-2). Large-scale manufacture of rhBMP-2 has associated production difficulties resulting from incomplete processing of the recombinant human protein due to insufficient endogenous levels of the paired basic amino acid cleaving enzyme (PACE) in CHO. In order to resolve this issue, CHO DUKX cells expressing rhBMP-2 were transfected with the soluble version of human PACE (PACEsol) resulting in improved amino-terminal homogeneity and a fourfold increase in rhBMP-2 productivity. In this article, we present a microarray expression profile analysis comparing the parental lineage to the higher producing subclone co-expressing PACEsol using a proprietary CHO-specific microarray. Using this technology we observed 1,076 significantly different genes in the high-productivity cells co-expressing PACEsol. Following further analysis of the differentially expressed genes, the Unfolded Protein Response (UPR) component of the endoplasmic reticulum stress response pathway was identified as a key candidate for effecting increased productivity in this cell system. Several additional ER- and Golgi-localised proteins were identified which may also contribute to this effect. The results presented here support the use of large-scale microarray expression profiling as a viable and valuable route towards understanding the behaviour of bioprocess cultures in?vitro.