Eukaryotic translation initiation factor 2 α phosphorylation as a therapeutic target in diabetes

Regulation of mRNA translation is of vital importance for a cell to adapt to environmental changes. To serve this purpose, intricate mechanisms controlling mRNA translation have evolved, of which the eukaryotic initiation factors eIF2 and eIF4 represent essential regulatory nodes for both stress sensing and signal transduction. Stress sensing by eIF2 α subunit (eIF2α) kinases, translation regulation by eIF2α subunit phosphorylation and subsequent dephosphorylation constitute a core molecular switch for stress adaptation and rapid metabolic regulation. It is not surprising; therefore, that dysfunction of such a pathway is implicated in human disease, especially metabolic syndrome and diabetes. In theory, therapeutic intervention to target the eIF2α phosphorylation pathway provides a promising therapeutic solution to tackle this debilitating syndrome. Careful evaluation of such therapies is crucially needed considering the central role of eIF2α pathway in cellular function for every organ.