TRANSCRIPTION FACTOR PU 1

这项建议的重点是转录的特征 因数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的相关因素 在85个氨基酸区域内。该区域作为DNA结合区域 并被命名为Ets结构域。原版 这个家族的成员是v-ETS，它是135kD融合蛋白的一部分 表达自禽白血病病毒E26。这种病毒被认为与 红系和髓系白血病在鸡中的发展。其他 这个家庭的成员也被认为与 白血病，包括PU1和Fli-1。这些结果强烈地表明， 许多Ets结构域蛋白参与了细胞的调控 扩散。 PU.1蛋白主要在巨噬细胞和B细胞中表达，并且 与具有5‘-GGAA-3’核心序列的富嘌呤序列结合。 PU1已被证明是一种转录激活因子，并可能参与 在免疫球蛋白轻链和重链基因的表达中 以及整合素CD11b。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 受PU调控的基因。1. 第一个具体目标是详细描述激活， 蛋白质-蛋白质相互作用和DNA结合域。基因突变 特定的氨基酸将被用来更清楚地定义结构域。 第二个特定目标是破坏ES细胞中的PU.1基因 小鼠通过同源重组。这些实验的结果将会有所帮助 确定PU1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 PU1的增强剂。我们建议找出独联体的代理元素 启动子，并表征与这些元件结合的蛋白质。我们 他们特别感兴趣的是PU是否。%1参与了监管 以及哪些DNA结合蛋白参与了PU1 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 PU1转录因子及其Ets结构域家族 转录因子。这些因素很可能起到重要作用 在造血系统内细胞谱系的发展中的作用。

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.