The long term objectives of this research proposal involve understanding the phenomenon of molecular compensation with respect to the fatty acid binding protein (FABP), keratinocyte lipid binding protein (KLBP). This gene is normally expressed in lens epithelial cells, and is found in low levels in several other tissues, but was first discovered as an upregulated message in skin carcinomas and papillomas. Additionally, KLBP has been found to be highly upregulated in adipose from mice containing a knockout of the adipocyte lipid binding protein (ALBP) gene. These cells have some mechanism to sense the change resulting from the lack of KLBP and compensate by inducing KLBP expression. This proposal focuses on understanding the regulation of KLBP in this latter condition. The first part involves cloning the KLBP gene in order to allow the study of the DNA sequences necessary for the upregulation of KLBP in primary adipocytes from mice lacking ALBP. The transcription factor(s) necessary for the upregulation of KLBP will be identified. It is hypothesized that the factors involved include the peroxisome proliferator activated receptors (PPAR), members of the steroid hormone supergene family. The results of the experiments will provide an understanding of the unique phenomenon of molecular compensation, as well as giving insights into the role of FABP in cancer cells, and the involvement of fatty acids in regulating gene expression through PPARs.
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