Translational regulation of GCN4 and the general amino acid control of yeast

被引:967
作者
Hinnebusch, AG [1 ]
机构
[1] NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA
关键词
protein synthesis; initiation factors; Gcn2; eIF2; eIF2B;
D O I
10.1146/annurev.micro.59.031805.133833
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Cells reprogram gene expression in response to environmental changes by mobilizing transcriptional activators. The activator protein Gcn4 of the yeast Saccharomyces cerevisiae is regulated by an intricate translational control mechanism, which is the primary focus of this review, and also by the modulation of its stability in response to nutrient availability. Translation of GCN4 mRNA is derepressed in amino acid-deprived cells, leading to transcriptional induction of nearly all genes encoding amino acid biosynthetic enzymes. The trans-acting proteins that control GCN4 translation have general functions in the initiation of protein synthesis, or regulate the activities of initiation factors, so that the molecular events that induce GCN4 translation also reduce the rate of general protein synthesis. This dual regulatory response enables cells to limit their consumption of amino acids while diverting resources into amino acid biosynthesis in nutrient-poor environments. Remarkably, mammalian cells use the same strategy to downregulate protein synthesis while inducing transcriptional activators of stress-response genes under various stressful conditions, including amino acid starvation.
引用
收藏
页码:407 / 450
页数:44
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