Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2)

Eukaryotic translation initiation factor 2 subunit 2 (EIF2S2), also known as eIF2β, is a critical component of the heterotrimeric eIF2 complex, which also includes alpha (EIF2S1) and gamma (EIF2S3) subunits [6, 14]. Its primary biological role is to facilitate the formation of the ternary complex with GTP and initiator methionyl-tRNA (Met-tRNAi), which is essential for the recruitment of the 40S ribosomal subunit to mRNA and the subsequent selection of the translation start codon [2, 6]. EIF2S2 also acts as a regulatory node in the Integrated Stress Response (ISR), where its activity is modulated by the phosphorylation of the eIF2α subunit, leading to a global reduction in protein synthesis to conserve cellular resources during stress [2, 16].\n\nIn the context of disease, EIF2S2 is frequently overexpressed in various malignancies, including glioblastoma, gastric cancer, and lung cancer, where it promotes tumor cell proliferation, migration, and survival by hijacking the translation machinery and regulating oncogenic pathways such as Wnt/β-catenin and PI3K/AKT/mTOR [1, 4, 30, 33]. Consequently, it has emerged as a promising therapeutic target; small molecules like tomatidine have been identified as inhibitors that can disrupt viral replication and suppress tumor growth [21, 25]. However, because EIF2S2 is fundamental to global protein synthesis, therapeutic strategies must carefully balance the inhibition of pathological translation with the maintenance of essential cellular functions to avoid systemic toxicity [3, 31].

Other names

eIF2-betaeIF2βEIF2BPPP1R67EIF2Eukaryotic translation initiation factor 2 subunit beta

Inhibition of translation initiation by disrupting ternary complex formation and modulating the Integrated Stress Response (ISR).