TRANSCRIPTION FACTOR PU 1

这一建议的重点是转录的表征 因子PU。1.这个因子属于一个不断增长的转录家族 基于高度序列同一性而相关的因子 在85个氨基酸区域内。这个区域作为DNA结合区 这些蛋白质的结构域，并已被命名为ETS结构域。原始 该家族的一个成员是v-ets，它是135 kD融合蛋白的一部分 表达自禽白血病病毒E26。这种病毒与 鸡的红细胞白血病和髓细胞白血病的发展。其他 这个家族的成员也与发展 白血病，包括PU.1和Fli-1。这些结果强烈表明 许多ETS结构域蛋白质参与细胞的调控， 增殖 PU.1蛋白主要在巨噬细胞和B细胞中表达， 与具有核心序列5 ′- GGAA-3 ′的富含嘌呤的序列结合。 PU.1已被证明是一种转录激活因子，并可能参与 免疫球蛋白轻链和重链基因的表达， 以及整合素CD 11b。此应用程序的总体设计是 定义PU的角色。1在转录调控和鉴定中的作用 这些基因由PU调控。1. 第一个具体目标是详细表征活化， 蛋白质-蛋白质相互作用和DNA结合域。突变 将使用特定的氨基酸来更清楚地限定结构域。 第二个具体目标是破坏ES细胞和ES细胞中的PU.1基因。 小鼠同源重组。这些实验的结果将有助于 确定PU.1在巨噬细胞分化和生长中的作用 和B细胞。我们还将寻找可能受PU.1调控的基因。 第三个具体目标是表征启动子和可能的 PU.1的增强子。我们建议鉴定其中的顺式作用元件 启动子和特征的蛋白质结合到这些元素。我们 尤其是对PU。1参与监管 以及哪些DNA结合蛋白参与PU.1 表达是巨噬细胞或B细胞特异性的。 该项目的长期目标是更好地了解 PU.1转录因子以及ETS结构域家族 转录因子这些因素可能起着重要作用。 在造血系统内细胞谱系发育中的作用。

The focus of this proposal is the characterization of the transcription factor PU. 1. This factor belongs to a growing family of transcription factors that are related based on a high degree of sequence identity within an 85 amino acid region. This region serves as the DNA binding domain for these proteins and has been named the ETS domain. The original member of this family was v-ets, which was part of a 135 kD fusion protein expressed from the avian leukemia virus E26. This virus has been linked to the development of both erythroid and myeloid leukemias in chickens. Other members of this family have also been linked to the development of leukemias, including PU.1 and Fli-1. These results strongly suggest that many of the ETS domain proteins are involved in the control of cell proliferation. The PU.1 protein is expressed primarily in macrophages and B cells, and binds to a purine rich sequence having a core sequence of 5' - GGAA-3'. PU.1 has been shown to be a transcriptional activator and may be involved in the expression of the immunoglobulin light and heavy chain genes as well as the integrin CD11b. The overall design of this application is to define the role of PU. 1 in the regulation of transcription and identify genes that are regulated by PU. 1. The first specific aim is to characterize in detail the activation, protein-protein interaction and the DNA binding domains. Mutation of specific amino acids will be used to define the domains more clearly. The second specific aim is to disrupt the PU.1 gene in ES cells and in mice by homologous recombination. Results from these experiments will help define the role of PU.1 in the differentiation and growth of macrophages and B cells. We will also look for genes that may be regulated by PU.1. The third specific aim is to characterize the promoter and possible enhancer of PU.1. We propose to identify the cis acting elements within the promoter and characterize the proteins that bind to these elements. We are particularly interested in whether PU. 1 is involved in the regulation of itself and which of the DNA binding proteins involved in PU.1 expression are macrophage or B cell specific. The long range goals of the project are to gain a better understanding of the PU.1 transcription factor as well as the family of ETS domain transcription factors. It is likely that these factors play an important role in the development of cell lineages within the hematopoietic system.