Gitlin S D, Dittmer J, Shin R C, Brady J N
Laboratory of Molecular Virology, National Cancer Institute, Bethesda, Maryland 20892.
J Virol. 1993 Dec;67(12):7307-16. doi: 10.1128/JVI.67.12.7307-7316.1993.
Transcription regulation of the oncogenic retrovirus human T-lymphotropic virus type I (HTLV-I) involves the composite activity of both viral and cellular transcription factors. The HTLV-I transforming protein, Tax1, modulates the activity of several cellular transcription factors, upregulating the level of viral gene expression. In addition, cellular transcription factors, such as Ets1, independently bind to the viral long terminal repeat in a sequence-specific manner and activate transcription. It was of interest to analyze the possible interaction of Tax1 and Ets1 in viral gene regulation. We now report that Tax1 and Ets1 increase expression from the HTLV-I promoter in a cooperative manner. The level of expression was increased 5- to 10-fold above the combined individual effect of Tax1 and Ets1. S1 nuclease analysis demonstrated that the cooperative effect was due to an increase in the levels of steady-state RNA. The functional interaction between Tax1 and Ets1 required the presence of the Tax1-responsive 21-bp repeat element TRE-1 and the Ets1-responsive element ERR-1. These results suggested the possible interaction of Ets1 with transcriptional regulatory proteins that bind to the 21-bp repeats. This interaction is demonstrated by decreased electrophoretic mobility of specific 21-bp repeat gel shift complexes in the presence of Ets1. Furthermore, interaction of Ets1 with the 21-bp repeat-binding proteins enhances the relative efficiency of binding to the DNA. This cooperative interaction between Ets1 and proteins which bind to the Tax1-responsive 21-bp repeats suggests a possible role for Ets1 in the regulation of viral gene expression.
致癌逆转录病毒人类嗜T淋巴细胞病毒I型（HTLV-I）的转录调控涉及病毒和细胞转录因子的复合活性。HTLV-I转化蛋白Tax1可调节多种细胞转录因子的活性，上调病毒基因表达水平。此外，细胞转录因子，如Ets1，以序列特异性方式独立结合病毒长末端重复序列并激活转录。分析Tax1和Ets1在病毒基因调控中可能的相互作用很有意义。我们现在报告，Tax1和Ets1以协同方式增加HTLV-I启动子的表达。表达水平比Tax1和Ets1单独作用的总和提高了5至10倍。S1核酸酶分析表明，协同效应是由于稳态RNA水平的增加。Tax1和Ets1之间的功能相互作用需要存在Tax1反应性21碱基重复元件TRE-1和Ets1反应元件ERR-1。这些结果提示Ets1可能与结合21碱基重复序列的转录调节蛋白相互作用。在Ets1存在的情况下，特定21碱基重复凝胶迁移复合物的电泳迁移率降低证明了这种相互作用。此外，Ets1与21碱基重复结合蛋白的相互作用增强了与DNA结合的相对效率。Ets1与结合Tax1反应性21碱基重复序列的蛋白之间的这种协同相互作用提示Ets1在病毒基因表达调控中可能发挥作用。
