Human eukaryotic translation initiation factor 4G (eIF4G) recruits Mnk1 tophosphorylate eIF4E

Human eukaryotic translation initiation factor 4E (eIF4E) binds to the mRNA cap structure and interacts with eIF4G, which serves as a scaffold protein for the assembly of eIF4E and eIF4A to form the eIF4F complex, eIF4E is an important modulator of cell growth and proliferation. It is the least abun dant component of the translation initiation machinery and its activity is modulated by phosphorylation and interaction with eIF4E-binding proteins (4 E-BPs), One strong candidate for the eIF4E kinase is the recently cloned MA PK-activated protein kinase, Mnk1, which phosphorylates eIF4E on its physio logical site Ser209 ill vitro. Here we report that Mnk1 is associated with the eIF4F complex via its interaction with the C-terminal region of eIF4G. Moreover, the phosphorylation of an eIF4E mutant lacking eIF4G-binding capa bility is severely impaired in cells. We propose a model whereby, in additi on to its role in eIF4F assembly, eIF4G provides a docking site for Mnk1 to phosphorylate eIF4E, We also show that Mnk1 interacts with the C-terminal region of the translational inhibitor p97, an eIF4G-related protein that do es not bind eIF4E, raising the possibility that p97 can block phosphorylati on of eIF4E by sequestering Mnk1.