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The integrated stress response. (A) The integrated stress response (ISR) converges on phosphorylation of eIF2α, resulting in global inhibition of cap-dependent mRNA translation. GCN2 is the relevant ISR-kinase upon translational arrest. Cap-independent pathways allow for the selective translation of ISR-specific mRNAs including ATF4. ATF4 is a transcription factor and effector of ISR that controls expression of stress response genes.
