%0 Journal Article
%T Identification of cellular pathways affected by Sortin2, a synthetic compound that affects protein targeting to the vacuole in Saccharomyces cerevisiae
%A Lorena Norambuena
%A Jan Zouhar
%A Glenn R Hicks
%A Natasha V Raikhel
%J BMC Chemical Biology
%D 2008
%I BioMed Central
%R 10.1186/1472-6769-8-1
%X In this study, we analyzed structure-function relationships of Sortin2 using structural analogues. The results show the key roles of sulphite substitution and a benzoic acid group. A Sortin 2 hypersensitivity screen for the induced secretion of a vacuolar cargo protein was done utilizing a yeast haploid deletion library. Using bioinformatics approaches, we highlighted functional information about the cellular pathways affected by drug treatment which included protein sorting and other endomembrane system-related processes.Chemical, genomic and genetics approaches were used to understand the mode of action of Sortin2, a bioactive chemical that affects the delivery of a vacuolar protein. Critical features of Sortin2 structure necessary for bioactivity suggest a binding pocket that may recognize two ends of Sortin2. The genome-wide screen shows that Sortin2 treatment in yeast affects primarily components within the endomembrane system. This approach allowed us to assign putative functions in protein sorting for fifteen genes of previously unknown function.Endomembrane trafficking in eukaryotes is essential for the intracellular delivery of cargoes and membranes. As the site of protein degradation, nutrient recycling and storage of biological components, the vacuole is one of the key compartments of the endomembrane system. In addition, the mechanisms implicated in the delivery of cargoes to the vacuole have been delineated mainly by yeast genetic screens. A relatively new approach for discovering cellular pathways that takes advantage of yeast genetics is chemical genomics, which uses small bioactive molecules that can affect biological pathways [2,3]. The physiological effects of such drugs may be appreciated and exploited long before the corresponding targets are identified. However, the eventual identification of target proteins within drug-sensitive pathways is necessary to discover and characterize intracellular networks [4-10].Using forward chemical genomics, we
%U http://www.biomedcentral.com/1472-6769/8/1