TRANSCRIPTIONAL ACTIVATION BY AD E1A AND HSV VP16

描述（改编自申请人摘要）：病毒转录 激活剂已经成为阐明 动物细胞中的转录调控。 我们一直在研究两种病毒 激活剂腺病毒（Ad）E1a和单纯疱疹病毒（HSV）VP16。 这些 有两种蛋白质是病毒复制所必需的， 特定病毒基因的转录。 在过去的一段时间里，我们 在理解这些机制方面取得了重大进展， 这两种病毒蛋白通过细胞因子激活 转录。 HSV VP16蛋白含有原型"酸性"激活结构域。 在过去的一段时间里，我们发现， VP16的功能是与一般转录因子直接相互作用 (GTF)TFIIB。 VP16-TFIIB相互作用促进了 TF11B进入preinitiation复合物。 实验被提议为 了解VP16-TFIIB相互作用及其在转录中的作用 激活，更详细。 与VP16一样，289aa的Ad E1a蛋白含有激活区。 几 观察表明，至少部分地， 通过与一种未知的细胞辅激活剂相互作用 实验 提出鉴定、分离和克隆这种细胞成分。 E1A是 不是序列特异性DNA结合蛋白，并且在过去的一段时间里， 我们发现E1a通过相互作用靶向启动子， 与几种类型的细胞DNA结合域。 我们将执行 实验来阐明如何与明显不同的蛋白质相互作用 主题实现了。 通过对E1a激活的研究，我们发现ATF家族的细胞 转录因子，它们参与多种转录因子的表达。 病毒和细胞激活的几个其他不同的代理。 实验 建议更详细地了解ATF-2的规定 转录活性

DESCRIPTION (Adapted from Applicant's Abstract): Viral transcriptional activators have been important tools to elucidate the mechanisms of transcriptional regulation in animal cells. We have been studying two viral activators adenovirus (Ad) E1a and Herpes Simplex Virus (HSV) VP16. These two proteins are essential for viral replication and function by stimulating transcription of specific viral genes. Over the past period of funding we have made significant progress in understanding the mechanisms by which these two viral proteins function through cellular factors to activate transcription. The HSV VP16 protein contains the prototype "acidic" activation domain. Over the past period of funding we have found that an important aspect of VP16 function is a direct interaction with the general transcription factor (GTF) TFIIB. The VP16-TFIIB interaction facilitates the recruitment of TF11B into the preinitiation complex. Experiments are proposed to understand the VP16-TFIIB interaction, and its role in transcription activation, in further detail. Like VP16, the 289aa Ad E1a protein contains an activation region. Several observations suggest that E1a function is mediated, at least in part, through interaction with an unidentified cellular co-activator. Experiments are proposed to identify, isolate and clone this cellular component. E1a is not a sequence-specific DNA binding protein, and over the past period of funding we have found that E1a is targeted to promoters through interaction with several types of cellular DNA binding domains. We will perform experiments to clarify how interaction with apparently diverse protein motifs is achieved. Through studies of E1a activation we discovered the ATF family of cellular transcription factors, which are involved in the expression of a variety of viral and cellular activation by several other, diverse agents. Experiments are proposed to understand in greater detail regulation of ATF-2 transcriptional activity.