Grant Christian, Nonnemacher Michael, Jain Pooja, Pandya Devanshi, Irish Bryan, Williams Simon C, Wigdahl Brian
Department of Microbiology and Immunology, The Pennsylvania State University, College of Medicine, Hershey, 17033, USA.
Virology. 2006 May 10;348(2):354-69. doi: 10.1016/j.virol.2005.12.024. Epub 2006 Feb 3.
CCAAT/enhancer-binding protein (C/EBP) basic region/leucine zipper (bZIP) transcription factors have been shown to form heterodimers with cAMP-responsive element binding protein 2 (CREB-2), a transcription factor involved in regulating basal and Tax-mediated transactivation of the human T cell leukemia virus type 1 (HTLV-1) long terminal repeat (LTR). In cells of the monocyte-macrophage lineage (proposed to play a role in HTLV-1 pathogenesis as an accessory target cell), several members of the C/EBP family are expressed at high levels and may have functional impact on both basal and Tax-mediated transactivation of the HTLV-1 LTR. Basal activation of the HTLV-1 LTR was enhanced by overexpression of C/EBPbeta, C/EBPdelta, or C/EBPepsilon, whereas transactivation of the LTR by Tax was inhibited by overexpression of C/EBPalpha and C/EBPbeta. Inhibition of Tax-mediated transactivation of the HTLV-1 LTR was co-activator-independent, did not require C/EBP binding to the Tax-responsive elements, and may involve heterodimerization with CREB factors.
CCAAT/增强子结合蛋白（C/EBP）碱性区域/亮氨酸拉链（bZIP）转录因子已被证明可与环磷酸腺苷反应元件结合蛋白2（CREB-2）形成异二聚体，CREB-2是一种参与调节人类1型T细胞白血病病毒（HTLV-1）长末端重复序列（LTR）基础转录及Tax介导的反式激活的转录因子。在单核细胞-巨噬细胞谱系的细胞中（该谱系被认为作为辅助靶细胞在HTLV-1发病机制中起作用），C/EBP家族的几个成员高水平表达，并且可能对HTLV-1 LTR的基础转录及Tax介导的反式激活产生功能性影响。C/EBPβ、C/EBPδ或C/EBPε的过表达增强了HTLV-1 LTR的基础激活，而C/EBPα和C/EBPβ的过表达抑制了Tax对LTR的反式激活。HTLV-1 LTR的Tax介导的反式激活的抑制不依赖于共激活因子，不需要C/EBP与Tax反应元件结合，并且可能涉及与CREB因子的异二聚化。
