ISP-1 is a naturally occurring immunosuppressant with a structure resembling that of sphingosine. ISP-1 inhibits serine palmitoyltransferase, the primary enzyme of sphingolipid biosynthesis and reduces intracellular sphingolipid, leading to cell death in mammalian cells and in yeast cells. To determine the mechanism underlying cell death induced by sphingolipid deprivation, ISP-1 resistant genes were isolated and characterized in yeast. Two genes were found to be tightly associated with sphingolipid signaling.
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