Eukaryotic initiation factor eIF2

eIF2 plays a central role in the maintenance of what is generally considered a rate-limiting step in mRNA translation. In this step, eIF2 binds GTP and Met-tRNA(i) and transfers Met-tRNA(i) to the 40S ribosomal subunit. At the end of the initiation process, GTP bound to eIF2 is hydrolyzed to GDP and the eIF2.GDP complex is released from the ribosome. The exchange of GDP bound to eIF2 for GTP is a prerequisite to binding Met-tRNA(i) and is mediated by a second initiation factor, eIF2B. In what is probably the best-characterized mechanism for the regulation of mRNA translation, phosphorylation of eIF2 on its smallest, or alpha-, subunit converts eIF2 from a substrate of eIF2B into a competitive inhibitor. Thus, phosphorylation of eIF2 alpha effectively prevents formation of the eIF2.GTP.Met-tRNA(i) complex and inhibits global protein synthesis. Phosphorylation of eIF2 alpha occurs under a variety of conditions including viral infection, apoptosis, nutrient deprivation, heme-deprivation, and certain stresses. (C) 1999 Elsevier Science Ltd. All rights reserved.