Biological Function of Basonuclin

描述（由申请方提供）：生物学功能研究 basonuclin。增加核糖体产量的能力对于 细胞增殖这对于角质形成干细胞尤其如此 因为它们必须不断分裂以维持细胞的正常内稳态， 组织，并且必须能够增加响应损伤的分裂速率。 Basonuclin是一种分子量为120 kDa的锌指蛋白，可能是一种转录调节因子。 从基础水平增强核糖体RNA转录的调节因子。 Basonuclin不同于先前描述的rRNA转录因子 因为它的表达是细胞类型特异性的和增殖相关的。我们 假设是basonuclin调节影响rRNA转录， 角质形成细胞中的核糖体产生，这种调节在 维持角质形成细胞的增殖能力。为了验证这一 根据这一假设，我们提出以下三个具体目标： 具体目标1，我们将研究，通过系统诱变和 在共转染测定中，将rRNA基因的启动子中的序列， 这是basonuclin的作用所必需的。我们还将使用诱变来定义 这些蛋白质结构域对于基底核蛋白的功能是重要的， rRNA转录激活因子。具体目标2，除了核糖体RNA 基因，basonuclin可以调节另一组基因。我们假设这 第二组包括编码核糖体蛋白的基因。我们将测试这个 假设通过确定是否basonuclin与启动子相互作用， 核糖体蛋白基因以及是否影响其转录。具体目标3， 我们将构建转基因小鼠，表达显性负突变， 基底角质形成细胞中的basonuclin。我们将检验这个突变体是否能 在体内抑制基底角质形成细胞中的Poll转录， 这种抑制对正常发育和维持的影响 表皮

DESCRIPTION (provided by the applicant): A study of the biological function of basonuclin. The ability to increase ribosome production is essential for cellular proliferation. This is particularly true for keratinocyte stem cells since they must divide continuously to maintain the normal homeostasis of the tissue and must be able to increase the rate of division in response to injury. Basonuclin, a zinc finger protein of 120 kDa, is likely to be a transcriptional regulator that enhances transcription of ribosomal RNA from a basal level. Basonuclin differs from the previously described rRNA transcription factors because its expression is cell type-specific and proliferation-related. Our hypothesis is that regulation of basonuclin affects rRNA transcription and ribosome production in keratinocytes and this regulation is important in maintaining the proliferative ability of keratinocytes. To test this hypothesis, we propose the following three specific aims: Specific Aim 1, We will investigate, by systematic mutagenesis and a co-transfection assay, the sequence (s) in the promoter of rRNA gene that is required for the action of basonuclin. We will also use mutagenesis to define the protein domains that are important for the function of basonuclin as an rRNA transcriptional activator. Specific Aim 2, In addition to ribosomal RNA genes, basonuclin may regulate another group of genes. We hypothesize that this second group includes genes encoding ribosomal proteins. We will test this hypothesis by determining if basonuclin interacts with the promoters of ribosomal protein genes and if it affects their transcription. Specific Aim 3, We will construct transgenic mice that express a dominant-negative mutation of basonuclin in the basal keratinocytes. We will examine if this mutant can inhibit Poll transcription in the basal keratinocytes in vivo and what are the effects of this inhibition on the normal development and maintenance of the epidermis.