Eukaryotic translation initiation factor 2 subunit 1 (eIF2α)

Eukaryotic translation initiation factor 2 subunit 1 (eIF2α, encoded by EIF2S1) is a component of the eIF2 complex that mediates the binding of initiator methionyl-tRNA to the ribosome in a GTP-dependent manner, a critical step in the initiation of eukaryotic protein synthesis[1][10]. Phosphorylation of eIF2α on serine 51 by one of four specialized kinases (PERK, GCN2, PKR, HRI) in response to diverse cellular stresses is a central regulatory mechanism of the integrated stress response, producing global translational repression while permitting selective translation of stress-protective mRNAs such as ATF4[4][6]. Persistent or dysregulated eIF2α phosphorylation has been implicated in a range of diseases including cancer, neurodegeneration, infectious diseases, and anemia[4][6]. The pathway is an important target of pharmacological intervention, generally through modulation of eIF2α kinases or regulatory phosphatases, rather than direct targeting of eIF2α itself.

Other names

eIF2αEIF2S1Eukaryotic initiation factor 2 alphaTranslation initiation factor eIF-2 subunit 1IF2A

Inhibition or activation of eIF2α kinases (PERK, PKR, GCN2, HRI) to modulate phosphorylation state of eIF2α; Inhibition of eIF2α dephosphorylation (e.g., via GADD34 modulators); Indirect modulation (e.g., ISRIB stabilizes eIF2B and restores translation in the presence of eIF2α phosphorylation)