Accumulation of phosphorylated sphingoid long chain bases results in cell growth inhibition in Saccharomyces cerevisiae.

Accumulation of phosphorylated sphingoid long chain bases results in cell growth inhibition in Saccharomyces cerevisiae.
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磷酸化鞘氨醇长链碱基的积累导致酿酒酵母细胞生长受到抑制。

DOI:
10.1093/genetics/156.4.1519
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发表时间:
2000
期刊:
影响因子:
3.3
通讯作者:
Saba,J
Saba,J
中科院分区:
生物学2区
文献类型:
--
作者:
Kim,S;Fyrst,H;Saba,J

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Sphingolipid metabolites in mammals can function as signaling molecules with cell-specific functions. InSaccharomyces cerevisiae, phosphorylated long chain bases, such as dihydrosphingosine 1-phosphate and phytosphingosine 1-phosphate, have also been implicated in stress responses. To further explore the biological roles of these molecules, we created disruption mutants forLCB4, LCB5, DPL1, YSR2, YSR3, andSUR2. LCB4andLCB5encode kinases that phosphorylate long chain bases.DPL1andYSR2/YSR3are involved in degradation of the phosphorylated long chain bases.SUR2catalyzes conversion of dihydrosphingosine to phytosphingosine. We adapted an HPLC method to measure intracellular concentrations of the phosphorylated long chain bases. Double mutants ofdpl1andysr2were inviable, whereasdpl1 ysr2 lcb4triple mutants were viable. Further, growth inhibition associated with accumulated phosphorylated long chain bases was observed in the triple mutantdpl1 ysr2 lcb4overexpressingLCB4orLCB5.These results indicate that phosphorylated long chain bases can inhibit cell growth. Mutants defective in bothYSR2andSUR2, which accumulated dihydrosphingosine 1-phosphate only, grew poorly. The phenotypes of theysr2 sur2mutants were suppressed by overexpression ofDPL1.Our results clearly show that elevated levels of phosphorylated long chain bases have an antiproliferative effect in yeast.
DOI: 10.1126/science.279.5356.1552
发表时间: 1998-03-06
期刊: SCIENCE
影响因子: 56.9
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