Interaction of human immunodeficiency virus type 1 Tat with a unique site of TFIID inhibits negative cofactor Dr1 and stabilizes the TFIID-TFIIA complex
Interaction of human immunodeficiency virus type 1 Tat with a unique site of TFIID inhibits negative cofactor Dr1 and stabilizes the TFIID-TFIIA complex
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DOI：
10.1128/jvi.70.8.5503-5510.1996
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发表时间：
1996-08-01
影响因子：
5.4
通讯作者：
Brady, JN
中科院分区：
文献类型：
--
作者：
Kashanchi, F;Khleif, SN;Brady, JN
我们之前报道了人类免疫缺陷病毒（HIV） 1型Tat蛋白与基础转录因子TBP/TFIID之间的直接物理相互作用。亲和层析表明，野生型Tat，而不是Tat的反激活突变体，能够从细胞提取物中消耗TBP/TFIID。这些实验首次证明了一种基础转录因子以依赖激活的方式与Tat结合。我们现在报道，在HIV 1型感染的细胞中可以检测到Tat-TBP相互作用。利用TBP的缺失和位点特异性突变体，从163到196个氨基酸定位了TBP与Tat相互作用的结构域。TBP的这个结构域包括H1和S2结构域，与其他激活蛋白（如E1A）的H2结合位点不同。Tat与TFIID的相互作用调节了辅助蛋白与TFIID的结合。这在凝胶移位试验中稳定了TFIID与TFIIA的相互作用。此外，Tat与TBP竞争Drl相互作用。但结果表明，基础转录因子TBP/TFIID是HIV转录的重要调控分子。
We have previously reported the direct physical interaction between the human immunodeficiency virus (HIV) type 1 Tat protein and the basal transcription factor TBP/TFIID. Affinity chromatography demonstrated that wild-type Tat, but not a transactivation mutant of Tat, was capable of depleting TBP/TFIID from cell extracts. These experiments represented the first demonstration of a basal transcription factor that binds, in an activation-dependent manner, to Tat. We now report that the Tat-TBP interaction can be detected in HIV type 1-infected cells. The domain of TBP interacting with Tat has been mapped from amino acids 163 to 196 by using deletion and site-specific mutants of TBP. This domain of TBP, which includes the H1 and S2 domains, is distinct from the H2 binding site for other activator proteins, such as E1A. The interaction of Tat with TFIID regulates the binding of accessory proteins to TFIID. Tat stabilizes the interaction of TFIID with TFIIA in a gel shift assay. In addition, Tat competes for Drl interaction with TBP. bur results suggest that the basal transcription factor TBP/TFIID represents an important regulatory molecule in HIV transcription.