A membrane transport defect leads to a rapid attenuation of translation initiation in Saccharomyces cerevisiae
A membrane transport defect leads to a rapid attenuation of translation initiation in Saccharomyces cerevisiae
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DOI：
10.1016/s1097-2765(04)00008-5
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发表时间：
2004-02-13
期刊：
影响因子：
16
通讯作者：
Linder, P
中科院分区：
文献类型：
--
作者：
Deloche, O;de la Cruz, J;Linder, P
脂质和蛋白质的转运是一个高度调控的过程，是维持真核细胞内各种细胞器完整性所必需的。酵母分泌途径的突变抑制rRNA、tRNA和核糖体蛋白基因的转录。在这里，我们表明，这些突变还会导致翻译启动的快速和特异的衰减，这种衰减发生在核糖体成分的转录抑制之前。利用不同的囊泡转运突变体和氯丙嗪，我们已经确定eIF2α激酶Gcn2p和eIF4E结合蛋白Eap1p是翻译衰减反应的主要介质。最后，在氯丙嗪处理的细胞中，这种反应不需要Wsc1p或蛋白激酶Pkc1p，这两者都位于核糖体成分转录抑制的上游。总而言之，我们的结果表明，酵母细胞不仅进化出一种转录调控，而且还进化出一种翻译调控，以确保在膜压力下蛋白质合成的有效衰减。
Transport of lipids and proteins is a highly regulated process, which is required to maintain the integrity of various intracellular organelles in eukaryotic cells. Mutations along the yeast secretory pathway repress transcription of rRNA, tRNA, and ribosomal protein genes. Here, we show that these mutations also lead to a rapid and specific attenuation of translation initiation that occurs prior to the transcriptional inhibition of ribosomal components. Using distinct vesicular transport mutants and chlorpromazine, we have identified the eIF2alpha kinase Gcn2p and the eIF4E binding protein Eap1p as major mediators of the translation attenuation response. Finally, in chlorpromazine-treated cells, this response does not require Wsc1p or the protein kinase Pkc1p, both of which are upstream of the transcriptional repression of ribosomal components. Altogether, our results suggest that yeast cells not only evolved a transcriptional but also a translational control to assure efficient attenuation of protein synthesis when membranes are stressed.