The role of Dlc-2 in ceramide signaling to PGP synthase
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The purpose of this project was to determine how Dlc-2 and Rho signaling modulate the ceramide induction of PGP synthase. This induction was studied at the transcriptional, post-transcriptional, and post-translational levels using cell culture, Real-Time RT-PCR, protein purification, phage display, and western blotting techniques. We have demonstrated that the PGP synthase gene is not controlled at the transcriptional level by ceramide and Rho, nor is the mRNA stability of PGP synthase affected. However, ceramide and Rho do seem to exhibit translational or post-translational control over the PGP synthase protein. The relationships between Dlc-2 (and Rho), ceramide, and PGP synthase (and CL) are important to understand. All three are involved in cancer and apoptotic responses. The knowledge gained by the experiments discussed in this thesis will contribute to an understanding of how these proteins and lipids interact. This knowledge may then be used in the future to develop cancer treatments.