EIF2A

EIF2A, eukaryotic initiation factor 2α, alias eIF2α. it is a key translation initiation factor that plays a central role in cellular stress response and regulation of protein synthesis. eIF2A is encoded by its own gene in human cells, and its mechanism of action involves the formation of a ternary complex by binding to GTP, which carries a Met-tRNAi that participates in the 43S pre-initiation complex (PIC) formation. Under appropriate conditions, the 43S PIC scans the mRNA for the initiation codon AUG to initiate the translation process. When cells experience stress, such as endoplasmic reticulum stress, amino acid starvation, or viral infection, EIF2A is phosphorylated by specific kinases, resulting in a blockage of its binding to eIF2B, which reduces the availability of the ternary complex and inhibits global protein synthesis, while promoting the selective translation of specific stress-associated mRNAs.

The biological significance of EIF2A is mainly reflected in its regulation of cellular stress response . Through phosphorylation, EIF2A is involved in a variety of signaling pathways, such as the endoplasmic reticulum stress-associated PERK-eIF2α-ATF4-CHOP signaling pathway and the GCN2-eIF2α pathway during amino acid starvation. Activation of these signaling pathways helps cells adapt to stress conditions, maintain protein homeostasis, and protect cells from damage. In addition, aberrant function of EIF2A has been associated with a variety of diseases, including certain types of cancer and neurodegenerative diseases, making it a potential target in drug development.