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Human T-lymphotropic virus tax activates human cytomegalovirus major-immediate early promoter and improves production of recombinant proteins in HEK293 cells

Authors

  • Teng Rhui Lwa,

    1. Expression Engineering Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01, Singapore 138668, Singapore
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  • Jialing Lee,

    1. Expression Engineering Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01, Singapore 138668, Singapore
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  • Chew Har Ng,

    1. Expression Engineering Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01, Singapore 138668, Singapore
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  • Qiao Jing Lew,

    1. Expression Engineering Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01, Singapore 138668, Singapore
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  • Hui Ching Hia,

    1. Animal Cell Technology Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01, Singapore 138668, Singapore
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  • Sheng-Hao Chao

    Corresponding author
    1. Expression Engineering Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01, Singapore 138668, Singapore
    2. NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119220, Singapore
    • Expression Engineering Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01, Singapore 138668, Singapore
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Abstract

The human cytomegalovirus (CMV) major immediate-early (MIE) promoter is widely used in mammalian cells for production of recombinant proteins. It is of great interest to further enhance protein production driven by the CMV promoter. Here, we report that the Tax protein of human T-lymphotropic virus stimulates the transgene expression under the control of CMV MIE promoter in HEK293 cells. At least threefold increases in transient production of recombinant proteins, including luciferase and two biopharmaceutical proteins (erythropoietin and interferon-γ), were detected. Furthermore, cyclic adenosine monophosphate (AMP)-response element binding protein 2 (CREB2) was identified as a cellular cofactor, which might be responsible for Tax transactivation of the CMV MIE promoter. Our results not only demonstrate the potential use of this novel expression strategy for improvement of recombinant protein production in HEK293 cells but also provide the molecular mechanism for Tax-mediated activation of CMV MIE promoter. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011

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