Abstract 1455 GCN2 eIF2 kinase as first responder in the integrated stress response

Diverse cellular stresses induce the integrated stress response (ISR), which features eIF2 phosphorylation and translational control that reprograms gene expression to alleviate cell damage and restore cell homeostasis. The eIF2 kinase GCN2 is a first responder in the ISR that is activated by starvation for amino acids and other stresses not directly related to nutrient limitations. This presentation will focus on the processes activating GCN2 during different stresses, the contributions of GCN2 in cancer progression, and the nature and therapeutic efficacy of small molecules that can be inhibitors or activators of GCN2.