Suppression of cap-dependent translation in mitosis

Cap-dependent translation is mediated by eIF4F, a protein complex composed of three subunits as follows: eIF4E, which recognizes the mRNA 5 ' cap stru cture; eIF4A, an RNA-helicase; and eIF4G, a scaffolding protein that binds eIF4E, eIF4A, and the eIF4E-kinase Mnk1 simultaneously. eIF4E is hypophosph orylated and cap-dependent translation is reduced at mitosis. Here, we show that 4E-BP1, a suppressor of eIF4E function, is also hypophosphorylated in mitosis, resulting in disruption of the eIF4F complex. Consequently, eIF4E is sequestered from the eIF4G/Mnk1 complex. These results explain the spec ific inhibition of cap-dependent translation in mitosis and also explain ho w eIF4E is rendered hypophosphorylated during mitosis. Furthermore, eIF4E i nteraction with eIF4GII is strongly decreased coincident with hyperphosphor ylation of eIF4GII. Thus, inhibition of cap-dependent translation in mitosi s results from a combination of phosphorylation modifications leading to eI F4F complex disruption.