Introduction to translational initiation factors and their regulation by phosphorylation

Regulation of gene expression frequently involves translational controls that operate at the level of the initiation phase. Initiation of protein synthesis in eukaryotes is promoted by greater than 10 initiation factors. Important among these are initiation factors eIF-2 and eIF-2B, which stimulate methionyl-tRNA binding to 40S ribosomal subunits, and eIF-4A, eIF-4B and eIF-4F, which stimulate mRNA binding. Many of the initiation factors are phosphorylated in vivo, and phosphorylation has been shown to regulate rates of global protein synthesis. Phosphorylation of eIF-2 on its α-subunit results in repression of translation by interfering with the recycling of the factor. Phosphorylation of eIF-4F on its α- and γ-subunits activates this limiting initiation factor and stimulates protein synthesis. Other initiation factor activities may also be regulated by phosphorylation, but these have not yet been characterized in detail. Regulating the translational activity of the cell by phosphorylation appears to be important in virus-infected cells and in the control of cell proliferation.