Interactions of the Eukaryotic Translation Initiation Factor eIF4E

Initiation of translation in eukaryotes is a highly regulated process by which a cell convinces the ribosome tostart protein synthesis. This involves a multitude of initiation factors that interact with the small ribosomal subunit, recruit the initiator tRNA, and enable binding of the43S particle to the messenger RNA (Sonenberg et al.2000). Recruitment of the ribosome to mRNA is thoughtto happen via binding of the eIF3 component of the 43Sribosomal complex to eIF4G. The latter protein binds tothe cap-binding protein eIF4E, recruiting the ribosome tothe 5′ end of the mRNA. Ribosome recruitment to mRNAis enhanced by the poly(A)-binding protein, Pabp, and ithas been shown in yeast that Pabp can mediate translationinitiation if the eIF4E/eIF4G interaction is impaired(Tarun et al. 1997). Using a third recruitment mechanism,some mRNAs have internal ribosome entry sites for direct recruitment of the small ribosomal subunit to themRNA, primarily in cooperation with eIF4G. Thus, theprotein eIF4G plays a central role in the initiation of eukaryotic translation. Mammalian and yeast forms ofeIF4G consist of about 1550 and 950 residues, respectively. A highly conserved segment consisting ofYxxxxLΦ (Φ stands for a hydrophobic residue) responsible for eIF4E binding has been identified. In addition,yeast and human eIF4G share related functionalities, suchas binding eIF4A, eIF3, and Pabp...