Gottlieb D, Heideman W, Saba J D
Children's Hospital Oakland Research Institute, California 94609-1809, USA.
Mol Cell Biol Res Commun. 1999 Apr;1(1):66-71. doi: 10.1006/mcbr.1999.0109.
Sphingosine-1-phosphate is a sphingolipid metabolite involved in the regulation of cell proliferation in mammalian cells. The major route of sphingosine-1-phosphate degradation is through cleavage at the C, bond by sphingosine phosphate lyase. The recent identification of the first dihydrosphingosine/sphingosine phosphate lyase gene in Saccharomyces cerevisiae establishes that phosphorylated sphingoid base metabolism is conserved throughout evolution. The dpl1delta deletion mutant, which accumulates endogenous phosphorylated sphingoid bases, exhibits unregulated proliferation upon approach to stationary phase. The increased proliferation rate during respiratory growth was associated with failure to appropriately recruit cells into the G1 phase of the cell cycle. Several genes were found to be overexpressed or prematurely expressed during nutrient deprivation in the dpl1delta strain, including glucose-repressible genes and G1 cyclins. These studies implicate a role for DPL1 and phosphorylated sphingoid bases in the regulation of global responses to nutrient deprivation in yeast.
鞘氨醇-1-磷酸是一种鞘脂代谢产物，参与哺乳动物细胞中细胞增殖的调控。鞘氨醇-1-磷酸降解的主要途径是通过鞘氨醇磷酸裂解酶在C键处进行裂解。最近在酿酒酵母中首次鉴定出二氢鞘氨醇/鞘氨醇磷酸裂解酶基因，这表明磷酸化鞘氨醇碱基代谢在整个进化过程中是保守的。dpl1δ缺失突变体积累内源性磷酸化鞘氨醇碱基，在接近稳定期时表现出不受调控的增殖。呼吸生长期间增殖速率的增加与未能将细胞适当地募集到细胞周期的G1期有关。在dpl1δ菌株中，发现几个基因在营养剥夺期间过度表达或过早表达，包括葡萄糖可抑制基因和G1细胞周期蛋白。这些研究表明DPL1和磷酸化鞘氨醇碱基在酵母对营养剥夺的全局反应调控中起作用。
