MOLECULAR ANALYSIS OF ALPHA CELL SPECIFIC UAS FUNCTION

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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.