TRANSCRIPTIONAL ACTIVATION BY AD E1A AND HSV VP16

描述(改编自申请者摘要)：病毒转录 激活剂已成为阐明其机制的重要工具。 动物细胞的转录调控。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 两种蛋白质对病毒复制和刺激功能是必不可少的 特定病毒基因的转录。在过去的一段时间里，我们为 已经在理解机制方面取得重大进展 这两种病毒蛋白通过细胞因子来激活 抄写。 单纯疱疹病毒VP16蛋白含有原型的“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互动促进招募 TF11B进入预引发复合体。建议进行实验，以 了解VP16-TFIIB的相互作用及其在转录中的作用 激活，更详细地说。 与VP16一样，289aa的Ad E1a蛋白含有一个激活区。几个 观察表明，E1a的功能至少部分地被介导， 通过与一种身份不明的细胞共激活剂相互作用。实验 被提议用来鉴定、分离和克隆这种细胞成分。E1a是 不是序列特异的DNA结合蛋白，在过去的一段时间里 我们发现E1a是通过互动面向推动者的 具有几种类型的细胞DNA结合域。我们将表演 阐明与明显不同的蛋白质如何相互作用的实验 主题就实现了。 通过对E1a激活的研究，我们发现了ATF家族的细胞 转录因子，参与多种转录因子的表达 病毒和细胞被其他几种不同的媒介激活。实验 建议更详细地了解ATF-2的规则 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.