CDK Phosphorylation of Translation Initiation Factors Couples Protein Translation with Cell-Cycle Transition

Protein translation in eukaryotes is cell-cycle dependent, with translation rates more robust in G1 phase of the cell cycle than in mitosis. However, whether the fundamental cell-cycle control machinery directly activates protein translation during the G1/S cell-cycle transition remains unknown. Using the early divergent eukaryote Trypanosoma brucei as a model organism, we report that the G1 cyclin-dependent kinase CRK1 phosphorylates two translation initiation factors, eIF4E4 and PABP1, to promote the G1/S cell-cycle transition and global protein translation. Phosphorylation of eIF4E4 by CRK1 enhances binding to the m⁷G cap structure and interaction with eIF4E4 and eIF4G3, and phosphorylation of PABP1 by CRK1 promotes association with the poly(A) sequence, self-interaction, and interaction with eIF4E4. These findings demonstrate that cyclin-dependent kinase-mediated regulation of translation initiation factors couples global protein translation with the G1/S cell-cycle transition.