PHOSPHORYLATION OF INITIATION FACTOR-2-ALPHA BY PROTEIN-KINASE GCN2 MEDIATES GENE-SPECIFIC TRANSLATIONAL CONTROL OF GCN4 IN YEAST
PHOSPHORYLATION OF INITIATION FACTOR-2-ALPHA BY PROTEIN-KINASE GCN2 MEDIATES GENE-SPECIFIC TRANSLATIONAL CONTROL OF GCN4 IN YEAST
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DOI：
10.1016/0092-8674(92)90193-g
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发表时间：
1992-02-07
期刊：
影响因子：
64.5
通讯作者：
HINNEBUSCH, AG
中科院分区：
文献类型：
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作者：
DEVER, TE;FENG, L;HINNEBUSCH, AG
我们发现真核生物翻译起始因子2 （eIF-2）的a亚基被蛋白激酶GCN2磷酸化，介导酵母转录激活因子GCN4的翻译控制。在体外，GCN2特异性磷酸化兔或酵母eIF-2的α亚基。在体内，eif -2- α的磷酸化在氨基酸饥饿的反应中增加，这依赖于GCN2。在体内和体外，用丙氨酸替代Ser-51消除了GCN2对eif -2- α的磷酸化，并消除了在氨基酸匮乏细胞中GCN4及其控制下的氨基酸生物合成基因的表达增加。Asp-51取代模拟磷酸化状态，在GCN2缺失的情况下抑制GCN4。因此，调节哺乳动物细胞中总蛋白合成的既定机制介导了酵母中基因特异性翻译控制。
We show that phosphorylation of the a subunit of eukaryotic translation initiation factor 2 (eIF-2) by the protein kinase GCN2 mediates translational control of the yeast transcriptional activator GCN4. In vitro, GCN2 specifically phosphorylates the alpha-subunit of rabbit or yeast eIF-2. In vivo, phosphorylation of eIF-2-alpha increases in response to amino acid starvation, which is dependent on GCN2. Substitution of Ser-51 with alanine eliminates phosphorylation of eIF-2-alpha by GCN2 in vivo and in vitro and abolishes increased expression of GCN4 and amino acid biosynthetic genes under its control in amino acid-starved cells. The Asp-51 substitution mimics the phosphorylated state and derepresses GCN4 in the absence of GCN2. Thus, an established mechanism for regulating total protein synthesis in mammalian cells mediates gene-specific translational control in yeast.