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KMID : 0624620180510080388
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BMB Reports
2018 Volume.51 No. 8 p.388 ~ p.393
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Understanding of the functional role(s) of the Activating Transcription Factor 4(ATF4) in HIV regulation and production
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Lee Seong-Deok
Yu Kyung-Lee
Park Seong-Hyun
Jung Yu-Mi
Kim Min-Jeong
You Ji-Chang
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Abstract
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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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KEYWORD
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Activating Transctiption Factor 4, ATF4, HIV-1, HIV-1 LTR, HIV-1 promoter, Transctiption activation
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