|Budget Amount *help
¥2,900,000 (Direct Cost : ¥2,900,000)
Fiscal Year 1998 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1997 : ¥1,800,000 (Direct Cost : ¥1,800,000)
In our previous study, the sphingosine-like immunosuppressant, ISP-1, was found to suppress proliferation of an interleukin-2-depentent cytotoxic T cell line, CTLL-2, through the inhibition of serine palmitoyltransferase, which catalyzes the committed step of sphingolipid biosynthesis. The growth inhibition induced by ISP-1 was antagonized by the addition of sphingosine. Instead of sphingosine, phytosphingsine is synthesized in the Saccharomyces cerevisiae by the similar pathway of mammalian cells, In this study, the inhibition of proliferation by ISP-1 was observed with Saccharomyces cerevisiae, and was abolished by addition of phytosphingsine. In addition, overreplication of DNA was detected in the ISP-1 treated yeast cells by flow cytometry. And we have identified a Saccharomyces cerevisiae gene, SLI2, that resisted the growth inhibition of ISP-1. The protein kinase catalytic domain is located at the carboxy-terminal portion of Sli2p. Kinase-dead mutants of SLI2 did not give any resistance to ISP-1, leading us to predict that kinase activity of Sli2p should be essential for its function in resisting ISP-1. Sli2p overexpression had no effect on serine palmitoyltransferase activity and sphingolipids metabolism. These results indicated that Sli2p may play an important role in rescuing yeast from decrease of sphingolipids induced by ISP-1.