Eukaryotic translation initiation factor 2 subunit 1 alpha (eIF2α)

Eukaryotic translation initiation factor 2 subunit 1 alpha (eIF2α; gene symbol EIF2S1) is the regulatory alpha subunit of the eIF2 heterotrimeric complex, which is essential for the initiation of protein synthesis in eukaryotes[1][7][12]. eIF2α binds GTP and the initiator methionine tRNA to form the ternary complex, which delivers initiator tRNA to the ribosome. Phosphorylation of Ser51 on eIF2α by stress-activated kinases converts eIF2 into an inhibitor of translation initiation, downregulating general protein synthesis while selectively promoting translation of stress-adaptive genes (such as ATF4)[1][5][11][12]. This regulatory mechanism is central to the integrated stress response (ISR) pathway and is implicated in a variety of diseases, including cancer, neurodegeneration, and infection[5][11][12]. Drugs that modulate the phosphorylation state of eIF2α or its effects on translation are under investigation as experimental therapeutics for several stress-related disorders.

Other names

EIF2S1eIF2 subunit alphaeIF2 alphaeIF2A (note: "eIF2A" is often confused but is a distinct protein [10]; primary alias is EIF2S1)

Inhibition of eIF2α dephosphorylation prolongs translation inhibition and upregulates stress response genes - Indirect reactivation of translation during cellular stress (e.g., ISRIB facilitates eIF2B function despite eIF2α phosphorylation)