REGULATION OF TRANSCRIPTION FACTOR F2F

蛋白质-蛋白质对转录因子活性的调节 相互作用已经成为转录调节的中心主题。 哺乳动物转录因子E2 F首先被描述为核转录因子。 结合腺病毒（Ad）E2 a启动子的活性。 的结合 E2 F与E2 a启动子中的反向重复序列的连接由Ad E4-6/7诱导 蛋白质，并与转录激活相关。 功能性E2 F 识别位点存在于细胞基因的启动子区域 参与细胞生长的调节。 E2 F与 抑制细胞增殖的细胞蛋白质（ 视网膜母细胞瘤RB.产品系列）随细胞的特定阶段而变化 周期 抑制细胞增殖，这是正常Rb功能的标志， 当Rb-E2 F相互作用因Rb突变而丧失时， 由DNA肿瘤病毒转化蛋白T抗原解离。 e1 a或 E7. 这表明E2 F是Rb信号通路的靶点， 转录调控与E2 F的分子机制之一 Rb的功能。 E2 F活性代表异二聚体 两个蛋白质家族成员的相互作用：E2 F蛋白和 DP蛋白。 这些蛋白质家族的特定成员已被证明 具有转化特性，并诱导S期进入和凋亡 当在细胞中过度表达时。 综上所述，这些结果表明， E2 F活性在细胞生长的调节中起核心作用。 的 蛋白质相互作用对E2 F活性的调节将不予解释 没有根据其蛋白质组分定义E2 F活性， 其监管约束性伙伴的功能。 具体目标是： 1. 比较E2 F-1和E2 F-4的功能和调节 作为受Rb和p107/p130调节的E2 F家族成员的范例， 分别为： 2. 为了研究Ad E4-6/7蛋白及其相关cdk 2在肿瘤细胞凋亡中的作用， E2 F-指导的转录的调节; 3. 分析Ad的细胞类似物的结构和功能 E4-6/7蛋白。

The modulation of transcription factor activity by protein-protein interaction has emerged as a central theme in transcriptional regulation. The mammalian transcription factor E2F was first described as a nuclear activity that binds to the adenovirus (Ad) E2a promoter. The binding of E2F to an inverted repeat in the E2a promoter is induced by the Ad E4-6/7 protein and correlates with transcriptional activation. Functional E2F recognition sites are present in the promoter regions of cellular genes involved in the regulation of cell growth. The association of E2F with cellular proteins that inhibit cell proliferation (members of the retinoblastoma. Rb. product family) varies with specific stages of the cell cycle. Inhibition of cell proliferation, a hallmark of normal Rb function, is relieved when the Rb-E2F interaction is lost by mutation of Rb or dissociated by the DNA tumor virus transforming proteins T-antigen. E1A or E7. This implicates E2F as a target in Rb signaling pathways and transcriptional regulation linked to E2F as one of the molecular mechanisms by which Rb functions. E2F activity represents the heterodimeric interaction of members of two protein families: the E2F proteins and the DP proteins. Specific members of these protein families have been shown to have transforming properties, and to induce S phase entry and apoptosis when overexpressed in cells. Taken together, these results suggest that E2F activity plays a central role in the regulation of cell growth. The regulation of E2F activity by protein interactions will not be explained without a definition of E2F activity in terms of its protein components and the function of its regulatory binding partners. The specific aims are: 1. To compare and contrast the function and regulation of E2F-1 and E2F-4 as paradigms of E2F family members that are regulated by Rb and p107/p130, respectively; 2. To study the role of the Ad E4-6/7 protein, and associated cdk2, in the regulation of E2F-directed transcription; 3. To analyze the structure and function of cellular analogues to the Ad E4-6/7 protein.