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

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...

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Bibliographic Details
Published in:Biotechnology progress 2011-05, Vol.27 (3), p.751-756
Main Authors: Lwa, Teng Rhui, Lee, Jialing, Ng, Chew Har, Lew, Qiao Jing, Hia, Hui Ching, Chao, Sheng-Hao
Format: Article
Language:English
Subjects:
Biological and medical sciences
Biotechnology
cyclic AMP-response element binding protein 2
cytomegalovirus
Cytomegalovirus - genetics
Deltaretrovirus - chemistry
Deltaretrovirus - genetics
erythropoietin
Fundamental and applied biological sciences. Psychology
Gene Products, tax - genetics
Gene Products, tax - physiology
Genes, Immediate-Early
HEK293 Cells
Human cytomegalovirus
human embryonic kidney 293
Human T-lymphotropic virus
human T-lymphotropic virus Tax
Humans
interferon-γ
major immediate-early promoter
Promoter Regions, Genetic - genetics
Recombinant Proteins - biosynthesis
Trans-Activators - genetics
Transgenes
Viral Proteins - genetics
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Summary: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
ISSN:8756-7938
1520-6033
1520-6033
DOI:10.1002/btpr.571