Tsuchiya H, Fujii M, Tanaka Y, Tozawa H, Seiki M
Department of Molecular Virology and Oncology, Kanazawa University, Japan.
Oncogene. 1994 Jan;9(1):337-40.
Tax1 of human T-cell leukemia virus type 1 (HTLV-1) is an enigmatic viral transactivator that regulates expression of the viral gene and also several cellular genes normally controlled by various mitogenic signals. However, previous studies have failed to define the functional domains of Tax1 for enhancer specificities and for transcriptional activation (95% of the protein portion was indispensable for the activation function). This complexity has hampered understanding of the molecular basis of Tax1 action. In this study, we analysed the activation function of a Tax1 fused to the heterologous DNA-binding domain of the yeast transcription factor GAL4 and dissected the domain required for the activation function by using derivatives of a Tax1 mutant with an insertion between amino acids (a.a.) 170 and 171. Analysis of the derivatives of the mutant fusion protein having various partial overlaps encompassing the interrupted site suggested that two contiguous stretches, AD-I (2-255 a.a.) and AD-II (227-337 a.a.), should be both intact for the activation function of Tax1 and that they form a functional activation domain.
人类嗜T细胞病毒1型(HTLV-1)的Tax1是一种神秘的病毒反式激活因子,它不仅调控病毒基因的表达,还调控一些通常受各种促有丝分裂信号控制的细胞基因的表达。然而,先前的研究未能确定Tax1增强子特异性和转录激活的功能结构域(95%的蛋白质部分对于激活功能是不可或缺的)。这种复杂性阻碍了对Tax1作用分子基础的理解。在本研究中,我们分析了与酵母转录因子GAL4的异源DNA结合结构域融合的Tax1的激活功能,并通过使用在氨基酸(a.a.)170和171之间有插入的Tax1突变体衍生物来剖析激活功能所需的结构域。对具有涵盖中断位点的各种部分重叠的突变融合蛋白衍生物的分析表明,两个相邻的片段,AD-I(2-255个氨基酸)和AD-II(227-337个氨基酸),对于Tax1的激活功能都应该是完整的,并且它们形成一个功能性激活结构域。