eIF4 initiation factors: Effectors of mRNA recruitment to ribosomes and regulators of translation

Eukaryotic translation initiation factor 4F (eIF4F) is a protein complex th at mediates recruitment of ribosomes to mRNA. This event is the rate-limiti ng step for translation under most circumstances and a primary target for t ranslational control. Functions of the constituent proteins of eIF4F includ e recognition of the mRNA 5' cap structure (eIF4E), delivery of an RNA heli case to the 5' region (eIF4A), bridging of the mRNA and the ribosome (eIF4G ), and circularization of the mRNA via interaction with poly(A)-binding pro tein (eIF4G). eIF4 activity is regulated by transcription, phosphorylation, inhibitory proteins, and proteolytic cleavage. Extracellular stimuli evoke changes in phosphorylation that influence eIF4F activity, especially throu gh the phosphoinositide 3-kinase (PI3K) and Ras signaling pathways. Viral i nfection and cellular stresses also affect eIF4F function. The recent deter mination of the structure of eIF4E at atomic resolution has provided insigh t about how translation is initiated and regulated. Evidence suggests that eIF4F is also implicated in malignancy and apoptosis.