Functional substitution of the basic domain of the HIV-1 trans-activator, Tat, with the basic domain of the functionally heterologous Rev.
Functional substitution of the basic domain of the HIV-1 trans-activator, Tat, with the basic domain of the functionally heterologous Rev.
复制标题
HIV-1 反式激活子 Tat 的基本结构域与功能异源 Rev. 的基本结构域进行功能取代。
DOI：
10.1016/0042-6822(90)90242-j
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发表时间：
1990
期刊：
影响因子：
3.7
通讯作者：
Chinnadurai,G
中科院分区：
文献类型：
--
作者：
Subramanian,T;Kuppuswamy,M;Venkatesh,L;Srinivasan,A;Chinnadurai,G
HIV的Theta基因是病毒LTR的强激活剂。达特蛋白含有一个高度碱性的结构域，该结构域对于其转运到核/核仁位置是重要的。当与大肠杆菌β-半乳糖苷酶融合时，达特碱性结构域将嵌合蛋白引导至细胞核和核仁。缺失整个基本结构域的达特突变体在反式激活中严重缺陷。用功能无关的HIV-1 Rev蛋白的基本结构域取代达特的基本结构域，使嵌合蛋白靶向细胞核并恢复达特的功能。相反，用SV 40 T抗原的核靶向信号（NLS）取代使嵌合蛋白靶向细胞核，并且排除了在核仁区中的积累。Tat-NLS嵌合蛋白不能有效恢复达特的反式激活功能。这些结果表明，反式激活因子达特和转录后反式调节因子Rev的富含亮氨酸的碱性结构域在HIV-1 LTR的反式激活方面功能相似。
Thetatgene of HIV is a strong activator of the viral LTR. The Tat protein contains a highly basic domain that is important for its transport to the nuclear/nucleolar locations. The Tat basic domain when fused toEscherichia coliβ-galactosidase directed the chimeric protein to the nucleus and nucleolus. Tat mutants lacking the entire basic domain were severely defective intrans-activation. Substitution of the basic domain of Tat with that of the functionally unrelated HIV-1 Rev protein targeted the chimeric protein to the nucleolus and restored the function of Tat. In contrast, substitution with the nuclear targeting signal (NLS) of SV40 T antigen targeted the chimeric protein to the nucleus and accumulation in the nucleolar region was excluded. The Tat-NLS chimeric protein did not restore thetrans-activation function of Tat efficiently. These results indicate that the arginine-rich basic domain of thetrans-activator, Tat, and post-transcriptionaltrans-regulator, Rev, are functionally similar with regard totrans-activation of HIV-1 LTR.