Regulation of Transcription Factor E2F

描述：（改编自研究者摘要）： 这项研究是为了了解如何调控基因表达， 特异性转录因子对细胞增殖能力的影响 和DNA肿瘤病毒的生长特性。我们研究的模型系统 是腺病毒对E2 F家族转录因子的调节 感染E2 F转录因子是调控细胞凋亡的关键因子。 增殖、凋亡和分化。E2 F的核心作用 家庭在调节细胞生长和死亡中的作用， 事实上，E2 F-视网膜母细胞瘤肿瘤抑制调节级联被发现， 几乎所有人类癌症中的突变或失调。E2 F过表达或 相反，E2 F表达的缺失促进动物中的肿瘤形成， E2 F在p53介导的凋亡调控中起关键作用。 因此，E2 Fs对基因表达的调节决定了生命或死亡 对细胞，并影响两个关键的生长抑制途径，Rb p53通路和p53通路。E2 F在多个层面受到监管， 不同的机制。E2 F调节的丧失导致细胞凋亡的诱导。 周期阻滞和凋亡。腺病毒蛋白影响许多过程 调节E2 F的活性。我曾以一种新奇的眼光， 腺病毒蛋白在三个不同区域对E2 F的调节。具体 该建议的目的是：1）确定腺病毒 感染增加E2 F蛋白水平并诱导细胞生长停滞; 2） 了解Ad E1 A和E4-6/7蛋白对E2 F反式激活的调节; 3）研究E1 A和E4-6/7蛋白对E2 F定位的调节作用。 这些研究将为分子机制提供新的见解 调节E2 F活性以及腺病毒蛋白如何影响细胞 和病毒生长特性。

DESCRIPTION: (Adapted from the Investigator's abstract): The broad objective of this research is to understand how the regulation of gene expression by specific transcription factors impacts on the proliferative capacity of cells and the growth properties of DNA tumor viruses. The model system that we study is the regulation of the E2F family of transcription factors by adenovirus infection. E2F transcription factors are key players in the regulation of proliferation, apoptosis, and differentiation. The central role that the E2F family plays in the regulation of cell growth and death is underscored by the fact that the E2F-retinoblastoma tumor suppressor regulatory cascade is found mutated or deregulated in virtually all human cancers. E2F over-expression or conversely the loss of E2F expression promotes tumor formation in animal models, and E2F plays a key role in the regulation of p53-mediated apoptosis. Thus, the regulation of gene expression by E2Fs makes life or death decisions for the cell, and impacts on two key growth suppression pathways, the Rb pathway and the p53 pathway. E2Fs are regulated at multiple levels and by different mechanisms. The loss of E2F regulation leads to the induction of cell cycle arrest and apoptosis. Adenovirus proteins impact on many of the processes that regulate E2F activity. We have made novel observations concerning the regulation of E2F by adenovirus proteins in three different areas. The specific aims of this proposal are: 1) To determine the mechanisms by which adenovirus infection increases E2F protein levels and induces cell growth arrest; 2) To understand the regulation of E2F transactivation by the Ad E1A and E4-6/7 proteins; and 3) To study the regulation of E2F localization by the Ad E1A and E4-6/7 proteins. The proposed studies will provide new insights into the molecular mechanisms that regulate E2F activity and how adenovirus proteins impact on both cellular and viral growth properties.