Rapamycin-induced Translational Derepression ofGCN4mRNA Involves a Novel Mechanism for Activation of the eIF2α Kinase GCN2

摘要: When starved for amino acids, Saccharomyces cerevisiae accumulates uncharged tRNAs to activate its sole eukaryotic initiation factor (eIF) 2α kinase GCN2. Subsequent phosphorylation of eIF2α impedes general translation, but translationally derepresses the transcription GCN4, which induces expression various biosynthetic genes elicit acid control response. By contrast, when supplied with enough nutrients, yeast activates target rapamycin signaling pathway stimulate translation by facilitating assembly eIF4F. A cross-talk was suggested between two pathways rapamycin-induced GCN4 mRNA. Here we show that causes an increase in phosphorylated derepress GCN4. This increment is not observed cells expressing mammalian non-GCN2 kinases place It thus does inhibit dephosphorylation rather activation seems require interaction and tRNAs, because rapamycin, similar starvation, fails induce GCN2 defective tRNA binding. However, contrast without increasing amount presumably modifying binding affinity