In mammalian cells, translation is controlled at the level of polypeptide chain initiation by eukaryotic initiation factors. The translation initiation factor 5 (eIF5) catalyzes the hydrolysis of GTP bound to the 40S ribosomal subunit, a function necessary for the subsequent joining of the 40S and 60S subunits to form the 80S initiation complex. eIF4E specifically binds to the mRNA cap to promote unwinding and exposure of the AUG-initiation codon. Overexpression of eIF4E can lead to cell transformation and tumorigenesis. An additional initiation factor, eIF2, is present as a heterotrimer composed of eIF2(alpha), eIF2(beta) and eIF2(gamma) subunits. This heterotrimer forms a complex with GTP and tRNA which then binds to the 40S ribosomal subunit. After the formation of the 80S initiation complex, eIF2 is hydrolyzed and eIF2-GDP is released from the complex. eIF2-GDP is subsequently converted to eIF2-GTP, a reaction catalyzed by eIF2B, and is then available to catalyze another round of initiation.