Role of cellular factors FUBP1 and DREF in regulation of viral and cellular gene expression via adenovirus E1A.

蜂窝监管网络本质上是冗余的，代表着一个抵抗中断的多节点无标度网络。这种类型的组织是必要的，以避免在单个节点中断时出现严重的网络故障。细胞调节网络的内在弱点在于网络功能的关键调节因子，即所谓的“中枢蛋白”。病原体已经进化出精妙的方法来瞄准这些枢纽，以重塑网络，使病原体繁殖和宿主逃脱。因此，利用病毒蛋白来重塑细胞提供了一种有用的手段来识别重要过程的关键细胞调节因子。我已经通过与腺病毒即刻早期基因产物E1a结合而鉴定出两种新的细胞调节因子：DREF和FUBP1。这两种蛋白质都鲜为人知，它们在细胞内的功能也是个谜。DREF是一种转录调节因子，参与细胞周期和生长控制基因的激活。FUBP1是一种蛋白质，它通过与基因调节区内的增强子结合，以及通过与mRNAs内的非翻译区相互作用来调节蛋白质翻译，从而在转录调控中发挥作用。腺病毒的E1a蛋白是一种由289个氨基酸组成的最大亚型的小蛋白。E1a可以被认为是一个“中枢探测器”，因为它有能力瞄准关键的细胞调节因子。E1a在研究和理解各种各样的细胞过程中一直是一个宝贵的工具。E1a由一个含有2个外显子的基因编码。外显子1编码E1a的一个区域，该区域已被发现与大量细胞蛋白结合，调节它们的功能。E1a的外显子2编码103个氨基酸，占E1a总大小的三分之一以上，但发现该区域结合的蛋白质很少。通过证明DREF和FUBP1与该区域内的E1a结合，我已经将结合到由外显子2编码的区域的有限蛋白质列表添加到了有限的蛋白质列表中。对E1a结合蛋白的研究不仅让我们了解了E1a，还让我们了解了与E1a结合的蛋白质。通过研究DREF和FUBP1及其与E1A的关联，我们将更多地了解它们的细胞功能以及为什么病毒蛋白以它们为靶标。

Cellular regulatory networks are inherently redundant, representing a multi-node scale-free network that is resistant to disruptions. This type of organization is necessary in order to avoid critical network failure upon disruption of a single node. The inherent weakness of a cellular regulatory network lies in key regulators of network function, known as "hub proteins". Pathogens have evolved exquisite ways in which to target these hubs in order to remodel the network and enable pathogen propagation and host evasion. Therefore, utilization of viral proteins that remodel the cell provides a useful means of identifying key cellular regulators of important processes. I have identified two novel cellular regulators by their virtue of binding to the adenovirus immediate early gene product E1A: DREF and FUBP1. Both of these proteins are poorly understood and their function within cells is enigmatic. DREF is a transcriptional regulator that is involved in activation of cell cycle and growth control genes. FUBP1 is a protein that appears to play a role in transcriptional regulation by binding to enhancers within gene regulatory regions as well as regulating protein translation by interacting with untranslated regions within mRNAs. The E1A protein of adenovirus is a small protein composed of 289 amino acids for the largest isoform. E1A can be considered a "hub detector" because of its ability to target key cellular regulators. E1A has been an invaluable tool in the study and understanding of a wide variety of cellular processes. E1A is encoded by a gene that contains 2 exons. Exon 1 codes for a region of E1A that has been found to bind to a large number of cellular proteins, modulating their function. Exon 2 of E1A encodes for 103 amino acids that comprise more than a third of the total size of E1A yet very few proteins have been found to bind in that region. I have added to the limited list of proteins binding to the region encoded by exon 2 by showing that DREF and FUBP1 bind to E1A within that region. Study of E1A-binding proteins teaches us not only about E1A but also about the proteins that bind to it. By studying DREF and FUBP1 and their association with E1A we will learn more about their cellular functions and why a viral protein targets them.