REGULATION OF YEAST PHO5 GENE

这项工作的长期目标是了解细胞如何感知和响应细胞外 信号。我们将研究芽殖酵母中重要的信号转导级联反应变化。 在胞外无机磷水平(“Pho”途径)。我们之前已经表明， 转录因子Pho4是磷酸盐反应信号转导途径的靶点，由 Pho80-Pho85细胞周期蛋白-细胞周期蛋白依赖性激酶(CDK)复合体和CDK抑制剂Pho81。我们 对这些成分的功能和调节了解很多，但对细胞的感觉知之甚少 磷酸盐水平并产生适当的生理反应。我们将重点介绍Pho如何 通路处理信息并协调对不同磷酸盐水平的反应。 除了与磷酸盐有关的细胞周期蛋白Pho80外，CDK Pho85还与9个细胞周期蛋白有关 新陈代谢。这些Pho85-Cyclin复合体调控的过程尚不清楚，主要是因为很少有 已经确定了与生理相关的底物。我们将采用一种新的方法来识别 蛋白激酶底物，目的是深入了解由 CDK照片85。 最终，磷酸盐信号到达细胞核，导致对磷酸盐反应的调节 PH05等基因。PH05基因的启动子是研究这种关系的一个很好的系统 基因调控和染色质结构之间的关系。我们最近确定了需要考虑的因素 改造PH05启动子染色质并观察到小分子(肌醇多聚磷酸) 规范这一过程。我们将重点了解染色质是如何在PH05启动子上重塑的 以及这一过程是如何受到监管的。 这些研究将提供对信号转导和转录调控机制的洞察， 在人类疾病和癌症中被错误调控的基本细胞生物学过程。

The long-term goal of this work is to understand how cells sense and respond to extracellular signals. We will study a signal transduction cascade in budding yeast important for responding to changes in the level of extracellular inorganic phosphate (the "Pho" pathway). We have previously shown that the transcription factor Pho4 is a target for a phosphate-responsive signal transduction pathway composed of the Pho80-Pho85 cyclin-cyclin dependent kinase (CDK) complex and the CDK inhibitor Pho81. We understand much about the function and regulation of these components, but little about how cells sense phosphate levels and generate an appropriate physiological response. We will focus on how the Pho pathway processes information and coordinates a response to different phosphate levels. The CDK Pho85 associates with nine cyclins, in addition to the cyclin Pho80 involved in phosphate metabolism. The processes regulated by these Pho85-cyclin complexes are unclear, largely because few physiologically-relevant substrates have been identified. We will employ a new method for identification of protein kinase substrates, with the goal of providing insight into the biological processes regulated by the CDK Pho85. Ultimately the phosphate signal reaches the nucleus, resulting in regulation of phosphate-responsive genes such as PH05. The promoter of the PH05 gene is an excellent system for studying the relationship between gene regulation and chromatin structure. We have recently identified factors which are required to remodel PH05 promoter chromatin and have observed that small molecules (inositol polyphosphates) regulate this process. We will focus on understanding how chromatin is remodeled at the PH05 promoter and how this process is regulated. These studies will provide insight into mechanisms of signal transduction and transcriptional regulation, basic cell biological processes which are misregulated in human diseases and cancer.