INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TAT ACTIVITY BY COEXPRESSION OF HETEROLOGOUS TRANS ACTIVATORS
INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TAT ACTIVITY BY COEXPRESSION OF HETEROLOGOUS TRANS ACTIVATORS
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DOI：
10.1128/jvi.66.4.2000-2007.1992
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发表时间：
1992-04-01
影响因子：
5.4
通讯作者：
DERSE, D
中科院分区：
文献类型：
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作者：
CARROLL, R;PETERLIN, BM;DERSE, D
我们通过使用人类免疫缺陷病毒 1 型 (HIV-1) 和马传染性贫血病毒 (EIAV) 的 Tat 蛋白的竞争实验研究了 Tat 介导的反式激活机制。 EIAV Tat 以及嵌合 EIAV/HIV-1 Tat 蛋白以细胞类型依赖性方式抑制 HIV-1 Tat 介导的反式激活。 此外，这些蛋白质抑制 Tat 噬菌体 R17 外壳蛋白嵌合体的反式激活。 抑制是由于效应子的激活域和竞争者之间对限制性细胞辅助因子的竞争而产生的。 竞争者激活域表达的背景影响了抑制的程度。 在转染的细胞中，EIAV Tat 和所有嵌合竞争者主要位于细胞质中，而 HIV-1 Tat 主要位于细胞核中。 这些数据与反式激活模型一致，其中 Tat 的激活结构域通过反式作用响应元件 (TAR) 与转录复合物结合并传递细胞因子。
We examined the mechanism of Tat-mediated trans activation through competition experiments employing Tat proteins of human immunodeficiency virus type 1 (HIV-1) and equine infectious anemia virus (EIAV). EIAV Tat, as well as chimeric EIAV/HIV-1 Tat proteins, inhibited HIV-1 Tat-mediated trans activation in a cell-type-dependent fashion. Furthermore, these proteins inhibited trans activation by Tat-bacteriophage R17 coat protein chimeras. Inhibition resulted from competition between activation domains of effectors and competitors for a limiting cellular cofactor. The context in which competitor activation domains were expressed contributed to the extent of inhibition. In transfected cells, EIAV Tat and all chimeric competitors were located primarily in the cytoplasm, whereas HIV-1 Tat was primarily located in the nucleus. These data are consistent with a model for trans activation in which the activation domain of Tat associates with and conveys a cellular factor to the transcription complex via the trans-acting-responsive element (TAR).