MOLECULAR ANALYSIS OF ALPHA CELL SPECIFIC UAS FUNCTION

了解基因表达的调控机制， 多肽激素是细胞生物学的关键问题之一。 的 了解这些机制对我们来说非常重要。 了解癌症、动脉粥样硬化、糖尿病和神经生理学。 最近已经很清楚，基本的细胞过程， 转录、生长控制和细胞内信号传导是保守的， 哺乳动物和酵母之间的区别 这提供了起诉工具的机会 以及酵母中可用的技术来研究问题和过程， 在物种间是保守的。 我的实验室先前已经证明哺乳动物的血清反应 因子，这是一种转录因子，参与调节细胞的增殖。 c-fos原癌基因，具有DNA结合特异性， 到酵母蛋白质。 这种酵母蛋白是MCM 1的产物 基因，并参与α细胞特异性UAS的功能， 酵母 在该提案中，提出了进一步的数据，以表明 MCM 1蛋白不仅参与细胞类型特异性的基因调控， 也是转录复合体的一部分， α-特异性基因对细胞外基质处理的反应 a交配因子 因此，MCM 1蛋白在信号转导中 途径类似于哺乳动物血清反应的方式 因子 为了进一步了解这些现象，本提案力求 追求三大具体目标。 (i)为了确定 α-特异性UAS PQ基序赋予细胞类型特异性基因 酵母中的调节。 (ii)来确定交配的分子基础 通过α细胞特异性UAS的基因表达的因子诱导。 (iii)为了确定哺乳动物之间的功能相似程度， SRF蛋白和MCM 1基因。 这项研究的结果应该有助于 对我们理解信号传导和细胞类型特异性基因 在酵母和哺乳动物细胞中的调节。

Understanding the mechanisms of regulation of gene expression by polypeptide hormones is one of the key problems in cell biology. The understanding of these mechanisms is of great importance to our understanding of cancer, atherosclerosis, diabetes, and neurophysiology. It has recently become clear that basic cellular processes involving transcription, growth control, and intracellular signalling are conserved between mammals and yeast. This provides the opportunity to sue the tools and techniques available in yeast to study problems and processes that are conserved across species. My laboratory has previously shown that the mammalian serum response factor, which is a transcription factor involved in the regulation of the c-fos proto-oncogene, has a DNA-binding specificity essentially identical to that of a yeast protein. This yeast protein is a product of the MCM1 gene, and participates in the functioning of alpha-cell-specific UAS's in yeast. In this proposal, further data is presented to indicate that the MCM1 protein not only participates in cell-type-specific gene regulation, but also is part of a transcription complex which is involved in the response of alpha-specific genes to treatment of cells with extracellular a-mating factor. Thus, the MCM1 protein is in a signal transduction pathway in a manner analogous to that of the mammalian serum response factor. In order to further understand these phenomena, this proposal seeks to pursue three broad specific aims. (i) To determine the mechanism by which the PQ motifs of alpha-specific UAS's confer cell-type-specific gene regulation in yeast. (ii) To determine the molecular basis for mating factor induction of gene expression through alpha-cell-specific UAS's. (iii) To determine the degree of functional similarity between mammalian SRF protein and the MCM1 gene. The results of this study should contribute to our understanding of signal transduction and cell-type-specific gene regulation in both yeast and mammalian cells.