Thus, PP2A activity plays a critical role in mediating ceramide signaling in eukaryotes. Our laboratory has recently discovered that yeast cells also require proper PP2A activity to initiate and progress normally through the terminal differentiation state of sporulation. When induced to sporulate, yeast diploids cells lacking PP2A activity initiate an invasive growth pattern rather than progress through meiosis. We are currently using genetic and biochemical approaches as a means to understand at the molecular level how PP2A activity regulates the sporulation process in yeast. We anticipate that some or all of the cell factors regulated by PP2A during sporulation will plays roles in ceramide signaling, as well.
Heart disease is responsible for over half of the deaths in the Western World.
Current therapeutic strategies aimed at preventing this disease focus on drugs that block or attenuate sterol synthesis. There are multiple regulatory mechanisms designed to maintain sterol homeostasis in eukaryotic cells. Our goal is to elucidate novel transcriptional mechanisms involved in sensing cellular sterol levels in order to test new sites for regulation of sterol levels in eukaryotic cells. Zymosterol is the immediate precursor of the major yeast sterol, ergosterol. Our data suggest that the transcription of these three genes is up-regulated by their substrates, the dimethylzymosterol to zymosterol intermediates.