COMPARATIVE ANALYSIS OF JUN PROTEIN FUNCTION

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The long term objective of the proposed research is to elucidate the role of the jun genes (c-jun, jun-B, and jun-D) in regulating cellular proliferation. Because little is presently known about the physiological consequences of jun gene expression, a broad approach is initially suggested. Specific objectives include comparing the transcriptional regulatory activity and oncogenic potential of the three Jun proteins. In addition, if functional differences manifest in these experiments, it is anticipated that it will be important to map the protein domains that contribute to differential activity because the information obtained may be useful in identifying the genes that Jun proteins regulate. Concomitantly, two approaches are described for studying the cellular and molecular consequences of jun gene expression. One strategy involves generating conditionally jun (-) cell lines through a regulable negatively complementing Jun protein. The other relies upon expression of a jun gene within its normal tissue compartments in a transgenic mouse strain. As this project develops, effort will be concentrated on the experiments that hold the most promise for identifying jun regulated genes.