Moriuchi M, Moriuchi H, Margolis D M, Fauci A S
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Baltimore, MD 21201, USA.
J Immunol. 1999 May 15;162(10):5986-92.
Transcription factors USF1 and USF2 up-regulate gene expression (i.e. , HIV-1 long terminal repeats) via interaction with an E box on their target promoters, which is also a binding site for c-Myc. The c-Myc oncoprotein is important in control of cellular proliferation and differentiation, while Yin-Yang 1 (YY1) has been shown to control the expression of a number of cellular and viral genes. These two proteins physically interact with each other and mutually inhibit their respective biological functions. In this study, we show that USF/c-Myc up-regulates, while YY1 down-regulates the promoter activity of CXCR4, a coreceptor for T cell-tropic HIV-1 entry. We have identified an E box around -260 and a YY1 binding site around -300 relative to the transcription start site. Mutation of the E box abolished USF/c-Myc-mediated up-regulation of CXCR4 promoter activity, and mutation of the YY1 binding site was associated with unresponsiveness to YY1-mediated inhibition. These data suggest that USF/c-Myc and YY1 may play an important role in the HIV-1-replicative cycle, by modulating both the viral fusion/entry process and viral expression.
转录因子USF1和USF2通过与靶启动子上的E盒相互作用上调基因表达（即HIV-1长末端重复序列），该E盒也是c-Myc的结合位点。c-Myc癌蛋白在细胞增殖和分化的控制中很重要，而阴阳1（YY1）已被证明可控制许多细胞和病毒基因的表达。这两种蛋白相互物理作用并相互抑制各自的生物学功能。在本研究中，我们表明USF/c-Myc上调，而YY1下调T细胞嗜性HIV-1进入的共受体CXCR4的启动子活性。我们在相对于转录起始位点约-260处鉴定出一个E盒和约-300处的一个YY1结合位点。E盒的突变消除了USF/c-Myc介导的CXCR4启动子活性上调，而YY1结合位点的突变与对YY1介导的抑制无反应相关。这些数据表明，USF/c-Myc和YY1可能通过调节病毒融合/进入过程和病毒表达，在HIV-1复制周期中发挥重要作用。
