Genetic manipulation of the protein synthetic capacity of mammalian cells

Heaton, Michele and Birch, John R. and Hovey, Alison and Kallmeier, Robert and Proud, Christopher G. and James, David C. (1999) Genetic manipulation of the protein synthetic capacity of mammalian cells. In: 16th Meeting of the European-Society-for-Animal-Cell-Technology (ESACT), Apr 25-29, 1999, Lugano, Switzerland. (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Major improvements in the yield of recombinant proteins produced by animal cell cultures are likely to result from an extension of productive cell lifetime. Genetic engineering of cell cycle and death mechanisms and /or improved fed-batch processes have been used to enhance cell productivity. In contrast, by direct genetic manipulation of the rate of protein synthesis in animal cells we intend to augment both cell specific production, and productive cell lifetime in batch culture. This approach also provides a means to increase the transient expression of recombinant proteins by ‘transient’ host cell engineering. mRNA translation initiation factors control the overall rate of protein synthesis. The phosphorylation state of a subset of these factors; 4E-BP1, eIF2B, eIF4G, eIF2 and eIF4E are important in the regulation of protein synthesis (Figure 1.). An increase in the phosphorylation state of the a subunit of eIF2 is associated with an inhibition of protein synthesis in response to stimuli such as heat shock (Duncan & Hershey, 1987), amino acid, glucose, or serum deprivation (Scorsone et al., 1987). The impairment of translation seen in response to heat shock is partially overcome by expression of a non-phosphorylatable mutant of eIF2α, Ser5lAla (Murtha-Riel et al., 1993). Thus, reduced rates of protein synthesis seen when cells encounter other such conditions are also expected to be attenuated by expression of this mutant, which is otherwise functional in translation.

Item Type: Conference or workshop item (Paper)
Subjects: Q Science
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences
Depositing User: I.T. Ekpo
Date Deposited: 07 Apr 1914 22:29
Last Modified: 07 Jul 2014 15:43
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