SLI1 (YGR212W) is a major gene conferring resistance to the sphingolipid biosynthesis inhibitor ISP-1, and encodes an ISP-1 N-acetyltransferase in yeast

摘要: ISP-1 (myriocin) is a potent inhibitor of serine palmitoyltransferase, the primary enzyme sphingolipid biosynthesis, and useful tool for studying biological functions sphingolipids in both mammals yeast (Saccharomyces cerevisiae). In previous study, we cloned multicopy suppressor genes ISP-1, one these, YPK1/SLI2, was shown to encode serine/threonine kinase which homologue mammalian SGK1 (serum/glucocorticoid-regulated 1). present another gene, termed SLI1 (YGR212W; GenBank accession number CAA97239.1), characterized. Sli1p has weak similarity Atf1p Atf2p, are alcohol acetyltransferases. Although sli1-null strain grew normally, IC50 growth this markedly decreased compared with that parental strain, indicating major contributor resistance yeast. On background, increase induced by YPK1 gene transfection almost abolished. These data indicate co-operates Ypk1p mediating found convert into N-acetyl-ISP-1 vitro. Furthermore, did not share ability inhibit cells, palmitoyltransferase inhibitory activity much lower than ISP-1. suggest inactivates due its N-acetyltransferase towards