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中的关键问题之一。这个 对这些机制的了解对我们的研究具有重要意义 了解癌症、动脉粥样硬化、糖尿病和神经生理学。 最近清楚的是，基本的细胞过程包括 转录、生长控制和细胞内信号传递是保守的 在哺乳动物和酵母之间。这为起诉这些工具提供了机会 以及酵母中可用来研究问题和过程的技术 在不同物种之间保存。 我的实验室之前已经表明，哺乳动物的血清反应 因子，这是一种转录因子，参与调节 C-fos原癌基因，具有基本相同的DNA结合特异性 相当于酵母蛋白。这种酵母蛋白是MCM1的产物 基因，并参与阿尔法细胞特异性UAS的功能 酵母。在这项提案中，提出了进一步的数据，以表明 MCM1蛋白不仅参与细胞类型特异性基因调控， 也是转录复合体的一部分，该复合体参与了 α-特异性基因对细胞外刺激的反应 A-交配因子。因此，MCM1蛋白处于信号转导过程中 途径的方式类似于哺乳动物的血清反应 因素。 为了进一步了解这些现象，本提案旨在 追求三个广泛而具体的目标。(I)决定采用何种机制 α-特异型UAS授予细胞类型特异型基因的PQ基序 酵母中的调节。(二)确定交配的分子基础 通过阿尔法细胞特异性UA诱导基因表达的因子。 (Iii)确定哺乳动物之间的功能相似性程度 SRF蛋白和MCM1基因。这项研究的结果应该有所贡献 对我们对信号转导和细胞类型特异性基因的理解 酵母和哺乳动物细胞的调节。

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.