Assessment of the Unfolded Protein Response Whole Genome Analysis in Sacchromyces Cerevisiae
Wood, Todd A
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Two compounds were examined for effects on the unfolded protein response and general cellular stress pathways in Saccharomyces cerevisiae. An overall characterization of genomic expression in response to treatment was accomplished. Drug treatment timecourses were analyzed for genetic or genomic regulation by RT-PCR and Affymetrix GeneChips respectively. RT-PCR yielded a timecourse for the drug interactions of selected pathways through representation by integral genes. Characterization by this method produced an induction timecourse of greater duration and larger magnitude than that represented by the GeneChip data. GeneChip data further indicated that both the Tunicamycin and Calcium Ionophore A23187 treatments (4µM) elicited increased expression of the UPR pathway as well as the STRE regulon based gene set, while the Ionophore further affected pathways involving inositol biosynthesis regulation. This supported previously derived data regarding these pathways, their regulation, and proposed modes of action of the compounds. Additional methods of representation provided genomic templates of the response, as well as the drugs' individual modes of action, such that these results may provide a unique way of identifying future inducers of the UPR in novel compound screens.