ANALYSIS OF TARGET GENES ACTIVATED--JUN ONCOPROTEIN

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The mechanisms governing the regulation of cell growth are fundamental to the understanding of tumorigenesis. These mechanisms include signal chains that can be affected by oncogenes. In order to analyze these mechanisms, one must know normal and aberrant functions of oncogenes, their targets and effects on cellular signalling. The long term objective of this work is to gain insight into the mechanisms by which oncogenes turn normal cells into cancer cells. The specific aims focus on the identification and molecular characterization of oncogenically important target genes activated by the jun oncoprotein. This knowledge will be invaluable in understanding the process by which oncogenes induce cell transformation as well as the steps involved in normal growth control. This study will be divided into three parts. The first involves the identification of primary target genes activated by jun. This will be done by subtraction screening of a cDNA library generated immediately after induction of expression of v-jun, against an uninduced library. The second area involves the determination of oncogenic potential of each target identified. This will be performed by assaying for cell transformation in the potential large number of targets, these assays will be performed with pools of DNA. Important targets from transformation positive pools can then be sorted out. The third area deals with a molecular analysis of oncogenically important target gene(s) and a structural and functional characterization of their products.