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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Understanding of the functional role(s) of the Activating Transcription Factor 4(ATF4) in HIV regulation and production

  • Lee, Seong-Deok (National Research Laboratory for Molecular Virology, Department of Pathology, School of Medicine, The Catholic University of Korea) ;
  • Yu, Kyung-Lee (National Research Laboratory for Molecular Virology, Department of Pathology, School of Medicine, The Catholic University of Korea) ;
  • Park, Seong-Hyun (National Research Laboratory for Molecular Virology, Department of Pathology, School of Medicine, The Catholic University of Korea) ;
  • Jung, Yu-Mi (National Research Laboratory for Molecular Virology, Department of Pathology, School of Medicine, The Catholic University of Korea) ;
  • Kim, Min-Jeong (Avixgen Inc.) ;
  • You, Ji-Chang (National Research Laboratory for Molecular Virology, Department of Pathology, School of Medicine, The Catholic University of Korea)
  • Received : 2018.03.13
  • Accepted : 2018.03.31
  • Published : 2018.08.31
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Abstract

The activating transcription factor (ATF) 4 belongs to the ATF/CREB (cAMP Response Element Binding bZIP [Basic Leucine Zipper]) transcription factor family, and plays a central role in the UPR (Unfolded Protein Response) process in cells. The induction of ATF4 expression has previously been shown to increase the replication of HIV-1. However, the detailed mechanism underlying this effect and the factors involved in the regulation of ATF4 function are still unknown. Here, we demonstrate first that knocking out ATF4 using siRNA shows a strong negative effect on HIV-1 production, indicating that ATF4 is a functional positive cellular factor in HIV-1 production. To determine the mechanism by which ATF4 regulates the HIV-1 life cycle, we assessed the effect of the overexpression of wild type ATF4 and its various derivatives on HIV-1 LTR-mediated transcriptional activation and the production of HIV-1 particles. This effect was studied through co-transfection experiments with either reporter vectors or proviral DNA. We found that the N-terminal domains of ATF4 are involved in HIV-1 LTR-mediated transcriptional activation, and thus in HIV-1 production.

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References

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