Mergia A, Renshaw-Gegg L W, Stout M W, Renne R, Herchenröeder O
Department of Medical Pathology, University of California, Davis 95616.
J Virol. 1993 Aug;67(8):4598-604. doi: 10.1128/JVI.67.8.4598-4604.1993.
The genome of simian foamy virus type 1 encodes a transcriptional transactivator (Taf) that dramatically elevates gene expression directed by the viral long terminal repeat. In this report, we describe the functional domains of simian foamy virus type 1 Taf. Several taf mutants and fusion proteins of Taf and the DNA-binding domain of the Saccharomyces cerevisiae transcriptional transactivator GAL4 were used in this study. Taf contains two potent activation domains. One of the activation domains is located at the amino terminus (positions 1 to 48, with position 1 representing the initiator amino acid methionine) and contains several acidic amino acids. The second activation domain was mapped to a region at the carboxy terminus (positions 277 to 300). These two domains activate gene expression directed by the viral long terminal repeat independently of each other. No significant amino acid sequence homology between the activation domains is noted. Thus, Taf belongs in part to the family of acidic transcriptional transactivators. The activation domain at the carboxy terminus is conserved among foamy virus transactivators but is not related to other known transcriptional activators. Therefore, the mechanism of gene activation by the carboxy terminus of Taf may be novel. In addition, a potential binding domain rich in basic amino acids (positions 179 to 222) and a highly conserved sequence among foamy virus transactivators (positions 93 to 109) were found to be critical for Taf activity.
1型猿猴泡沫病毒的基因组编码一种转录反式激活因子(Taf),该因子可显著提高由病毒长末端重复序列指导的基因表达。在本报告中,我们描述了1型猿猴泡沫病毒Taf的功能结构域。本研究使用了几种Taf突变体以及Taf与酿酒酵母转录反式激活因子GAL4的DNA结合结构域的融合蛋白。Taf包含两个有效的激活结构域。其中一个激活结构域位于氨基末端(第1至48位,第1位代表起始氨基酸甲硫氨酸),含有几个酸性氨基酸。第二个激活结构域定位在羧基末端的一个区域(第277至300位)。这两个结构域彼此独立地激活由病毒长末端重复序列指导的基因表达。激活结构域之间未发现明显的氨基酸序列同源性。因此,Taf部分属于酸性转录反式激活因子家族。羧基末端的激活结构域在泡沫病毒反式激活因子中是保守的,但与其他已知的转录激活因子无关。因此,Taf羧基末端激活基因的机制可能是新颖的。此外,发现一个富含碱性氨基酸的潜在结合结构域(第179至222位)以及泡沫病毒反式激活因子中高度保守的序列(第93至109位)对Taf活性至关重要。