eIF4E-binding proteins: new factors, new locations, new roles

The cap-binding translation initiation factor eIF4E (eukaryotic initiation factor 4E) is central to protein synthesis in eukaryotes. As an integral component of eIF4F, a complex also containing the large bridging factor eIF4G and eIF4E RNA helicase, eIF4E enables the recruitment of the small ribosomal subunit to the 5' end of mRNAs. The interaction between eIF4F and eIF4F via a YXXXXL phi motif is regulated by small eIF4F-binding proteins, 4E-BPs, which use the same sequence to competitively bind eIF4F thereby inhibiting cap-dependent translation. Additional eIF4F-binding proteins have been identified in the last 10-15 years, characterized by the YXXXXL phi motif, and by interactions (many of which remain to be detailed) with RNA-binding proteins, or other factors in complexes that recognize the specific mRNAs. In the present article, we focus on the metazoan 4E-T (4E-transporter)/Cup family of eIF4F-binding proteins, and also discuss very recent examples in yeast, fruitflies and humans, some of which predictably inhibit translation, while others may result in mRNA decay or even enhance translation; altogether considerably expanding our understanding of the roles of eIF4F-binding proteins in gene expression regulation.