Polyribosome Binding by GCN1 Is Required for Full Activation of Eukaryotic Translation Initiation Factor 2α Kinase GCN2 during Amino Acid Starvation

Point mutations in two segments of GCN1 lead to a greater reduction in polyribosome binding and a stronger decrease in protein phosphorylation.

• Activation of the protein kinase GCN2 is mediated by uncharged tRNAs in starved cells.
• GCN2 requires interaction with the GCN1.GCN20 complex and ribosomes for its function.
• Mutations in GCN1 reduce its ability to bind to polyribosomes without affecting its overall expression.
• Simultaneous mutations in GCN1 segments result in a stronger decrease in eukaryotic translation initiation factor 2alpha phosphorylation compared to single mutations.
• A specific mutation in the GCN1 domain significantly impairs GCN2 activation beyond its impact on ribosome binding.

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