Figure 1.

Phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α) regulates global and gene-specific translation. The eIF2α kinases general control nonderepressible 2 (GCN2) and protein kinase R (PKR)-like endoplasmic reticulum (ER) kinase (PERK) are activated by nutritional stress or perturbations in the ER, respectively. Type 1 protein phosphatase complex (PP1c) combines with CReP to dephosphorylate eIF2α during basal conditions and GADD34 in feedback control of the integrated stress response (ISR). Phosphorylation of eIF2α reduces global translation initiation coincident with preferential translation of ATF4, encoding a basic zipper (bZIP) transcriptional activator that dimerizes with other transcript factors to regulate transcription of ISR genes that function in adaptation to stress.