Sphingoid base is required for translation initiation during heat stress in Saccharomyces cerevisiae
Sphingoid base is required for translation initiation during heat stress in Saccharomyces cerevisiae
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DOI：
10.1091/mbc.e05-11-1039
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发表时间：
2006-03-01
影响因子：
3.3
通讯作者：
Riezman, H
中科院分区：
文献类型：
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作者：
Meier, KD;Deloche, O;Riezman, H
鞘脂是许多细胞功能所必需的，包括对热休克的反应。我们分析了酵母lcb1-100突变体，该突变体在鞘脂生物合成的第一步条件受损，显示出热休克蛋白合成和活力的强烈下降。热休克蛋白mrna的转录和核输出不受影响。然而，在热应激条件下，lcb1-100细胞由于翻译起始缺陷而表现出蛋白质合成的强烈减少。必需的脂质是鞘基，而不是神经酰胺或鞘基磷酸盐。lcb-100细胞中eif4e结合蛋白Eap1p的缺失恢复了热休克蛋白的翻译并提高了生存能力。lcb1-100在热胁迫下的翻译缺陷至少部分是由于鞘碱激活的PKH1/2蛋白激酶的功能降低。此外，在lcb1-100细胞中观察到翻译起始因子eIF4G的缺失，泛素的过度表达允许热应激后翻译的部分恢复。综上所述，我们已经证明了在热休克恢复过程中对鞘基的需求，并表明这反映了一个直接的脂质依赖信号给帽依赖的翻译起始装置。
Sphingolipids are required for many cellular functions including response to heat shock. We analyzed the yeast lcb1-100 mutant, which is conditionally impaired in the first step of sphingolipid biosynthesis and shows a strong decrease in heat shock protein synthesis and viability. Transcription and nuclear export of heat shock protein mRNAs is not affected. However, lcb1-100 cells exhibited a strong decrease in protein synthesis caused by a defect in translation initiation under heat stress conditions. The essential lipid is sphingoid base, not ceramide or sphingoid base phosphates. Deletion of the eIF4E-binding protein Eap1p in lcb-100 cells restored translation of heat shock proteins and increased viability. The translation defect during heat stress in lcb1-100 was due at least partially to a reduced function of the sphingoid base-activated PKH1/2 protein kinases. In addition, depletion of the translation initiation factor eIF4G was observed in lcb1-100 cells and ubiquitin overexpression allowed partial recovery of translation after heat stress. Taken together, we have shown a requirement for sphingoid bases during the recovery from heat shock and suggest that this reflects a direct lipid-dependent signal to the cap-dependent translation initiation apparatus.