The broad aim of this research is to determine the mechanism by which hormones regulate the expression of the gene for cytosolic P-enolpyruvate carboxykinase from the rat. This will involve the further characterization of the 5'-flanking sequences which contain regulatory regions responsive to cAMP and other hormones and the identification of areas of the gene involved in its tissue specific expression. We also plan to isolate and identify factors which may be involved as intermediates in the regulation of P-enolpyruvate carboxykinase gene expression. Specific major goals of our program will be to: 1. Identify sequences responsible for regulation of P-enolpyruvate carboxykinase gene expression by cAMP, insulin and glucocorticoids. 2. Determine intermediates in the hormonal regulation of transcription of the P-enolpyruvate carboxykinase gene using in vitro transcription assays. 3. Study the maturation and turnover of P-enolpyruvate carboxykinase mRNA. 4. Identify sequences responsible for the tissue specific regulation of the P-enolpyruvate carboxykinase gene. Our long term objective is to extend our knowledge of the hormonal regulation of P-enolpyruvate carboxykinase gene expression especially in diseases such as diabetes. We also plan to develop new procedures for introducing functional copies of this gene in mammalian cells in order to study its effect on metabolic pathways in specific tissue.
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