REGULATION OF TRANSCRIPTION FACTOR F2F

蛋白质-蛋白质对转录因子活性的调节 相互作用已成为转录调控的中心主题。 哺乳动物转录因子E2F最先被描述为核 与腺病毒(Ad)E2a启动子结合的活性。的约束性 AdE4-6/7诱导E2F为E2A启动子中的反向重复序列 蛋白质，并与转录激活相关。功能正常的E2F 识别位点存在于细胞基因的启动子区域 参与调节细胞生长的。E2F与 抑制细胞增殖的细胞蛋白( 视网膜母细胞瘤。RB。产品系列)随细胞的特定阶段而不同 周而复始。抑制细胞增殖，这是正常Rb功能的标志， 当Rb-E2F相互作用因Rb或Rb突变而丢失时 被DNA肿瘤病毒转化蛋白T抗原解离。E1a或 E7。这意味着E2F是RB信号通路和 转录调控与E2F相关的分子机制之一 RB通过它来发挥作用。E2F活性代表异二聚体 两个蛋白质家族成员的相互作用：E2F蛋白和 DP蛋白。这些蛋白质家族的特定成员已经被证明是 具有转化特性，并诱导S进入时相并诱导细胞凋亡 当在细胞中过度表达时。总而言之，这些结果表明 E2F活性在细胞生长调控中起着核心作用。这个 不会解释蛋白质相互作用对E2F活性的调节 没有根据其蛋白质成分来定义E2F活性以及 其具有监管约束力的伙伴的职能。具体目标是： 1.比较和对比E2F-1和E2F-4的功能和调节 作为受Rb和p107/p130调控的E2F家族成员的范例， 分别； 2.研究AdE4-6/7蛋白及其相关的CDK2蛋白在小鼠卵巢癌中的作用。 调控E2F定向转录； 3.分析Ad.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.