eIF3i regulation of protein synthesis, cell proliferation, cell cycle progression, and tumorigenesis

eIF3i, a 36-kDa protein, is a putative subunit of the eIF3 complex important for translation initiation of mRNAs. It is a WD40 domain-containing protein with seven WD40 repeats that forms a β-propeller structure with an important function in pre-initiation complex formation and mRNA translation initiation. In addition to participating in the eIF3 complex formation for global translational control, eIF3i may bind to specific mRNAs and regulate their translation individually. Furthermore, eIF3i has been shown to bind to TGF-β type II receptor and participate in TGF-β signaling. It may also participate in and regulate other signaling pathways including Wnt/β-catenin pathway via translational regulation of COX-2 synthesis. These multiple canonical and noncanonical functions of eIF3i in translational control and in regulating signal transduction pathways may be responsible for its role in cell differentiation, cell cycle regulation, proliferation, and tumorigenesis. In this review, we will critically evaluate recent progresses and assess future prospects in studying eIF3i.