eIF5 is a dual function GAP and GDI for eukaryotic translational control

We recently showed in a publication in Nature that the eukaryotic translation initiation factor eIF5 has a second regulatory function and is a GDI (GDP dissociation inhibitor) in addition to its previously characterized role as a GAP (GTPase accelerating protein). These findings provide new insight into the mechanism of translation initiation in eukaryotic cells. Additional findings show that the GDI function is critical for the normal regulation of protein synthesis by phosphorylation of eIF2α at ser51. Because eIF2 phosphorylation is a ubiquitous mode of translational control these results are of broad interest. Here we review these and related studies and suggest they offer further evidence of parallels between the functions of regulators of the translation factor eIF2 and both heterotrimeric and small GTPases. © 2010 Landes Bioscience.