Elucidation of the regulatory mechanisms for cell growth and apoptosis is important for understanding the molecular basis for normal cell development and neoplasm. This proposed research focuses on the role of an animal lectin, galectin-3, in regulation of cell growth and apoptosis. This protein is upregulated in various neoplasms and the investigator has recently obtained data supporting its role in regulation of cell growth and apoptosis. He discovered that galectin-3 has striking sequence similarity with Bcl-2, a well characterized cell death repressor and that galectin-3 binds Bcl-2. He proposes to pursue the following three specific aims: 1. Establishment of the anti-apoptotic activity of galectin-3. He will establish the generality of galectin-3's anti-apoptotic activity by testing galectin-3 expressing transfectants generated from various cell types and exposed to different apoptotic stimuli. He will firmly establish the anti-apoptotic activity of galectin-3 by using several approaches including the use of galectin-3-deficient mice. He will also cross-breed mice transgenic for tax, which develop lymphomas spontaneously, and the galectin-3-deficient mice to determine whether expression of the lectin has any effect on lymphoma development. 2. Elucidation of the molecular basis for galectin-3's anti-apoptotic activity. The regulation of cell cycle progression by galectin-3 will be studied. The relationship of galectin-3 to other components in cell death pathways will be investigated. The subcellular localization of galectin-3 in relationship to its anti-apoptotic activity will be determined. Structure-function relationship of galectin-3 will be analyzed to identify regions in galectin-3 that are critical for its anti-apoptotic activity. 3. Identification of target proteins involved in galectin-3's anti-apoptotic activity. The relevance of galectin-3/Bcl-2 interaction to galectin-3's anti-apoptotic activity will be investigated. Other partners of galectin-3 that may be responsible for this lectin's intracellular functions will be identified.
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