National Research Laboratory for Molecular Virology, Department of Pathology, School of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
Avixgen Inc., Seoul 06649, Korea.
BMB Rep. 2018 Aug;51(8):388-393. doi: 10.5483/bmbrep.2018.51.8.054.
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. [BMB Reports 2018; 51(8): 388-393].
激活转录因子 4（ATF4）属于 ATF/CREB（cAMP 反应元件结合 bZIP [碱性亮氨酸拉链]）转录因子家族，在细胞中的未折叠蛋白反应（UPR）过程中发挥核心作用。先前已经表明，ATF4 表达的诱导会增加 HIV-1 的复制。然而，这种效应的详细机制以及调节 ATF4 功能的因素仍不清楚。在这里，我们首先证明使用 siRNA 敲除 ATF4 对 HIV-1 的产生有很强的负作用，这表明 ATF4 是 HIV-1 产生中的功能性正向细胞因子。为了确定 ATF4 调节 HIV-1 生命周期的机制，我们评估了野生型 ATF4 及其各种衍生物对 HIV-1 LTR 介导的转录激活和 HIV-1 颗粒产生的影响。通过与报告载体或前病毒 DNA 的共转染实验研究了这种效应。我们发现，ATF4 的 N 端结构域参与了 HIV-1 LTR 介导的转录激活，从而参与了 HIV-1 的产生。[BMB 报告 2018；51(8):388-393]。
