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

• Published in: Cell reports (Cambridge) 2018-12, Vol.25 (11), p.3204-3214.e5
• Main Authors: An, Tai, Liu, Yi, Gourguechon, Stéphane, Wang, Ching C., Li, Ziyin
• Format: Article
• Language: English
• Subjects: CDC2 Protein Kinase; Cell Cycle; Cyclin-Dependent Kinases - metabolism; Eukaryotic Initiation Factor-4E - metabolism; Guanine - analogs & derivatives; Guanine - metabolism; Phosphorylation; Poly A - metabolism; Poly(A)-Binding Protein I - metabolism; Protein Binding; Protein Biosynthesis; Protozoan Proteins; RNA Caps - metabolism; Substrate Specificity; Trypanosoma brucei brucei - metabolism
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2018.11.063

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. [Display omitted] •CRK1 phosphorylation of eIF4E4 and PABP1 promotes the G1/S cell-cycle transition•Binding of eIF4E4 to the m7G cap is enhanced by CRK1-mediated phosphorylation•Phosphorylation of PABP1 by CRK1 promotes its association with the poly(A) sequence•Phosphorylation of eIF4E4 and PABP1 couples translation with the cell-cycle transition Protein translation is cell-cycle dependent, with more robust translation rates in the G1 phase of the cell cycle than in mitosis. An et al. show that the G1 cyclin-dependent kinase CRK1 phosphorylates translation initiation factors eIF4E4 and PABP1 to couple protein translation initiation with the G1/S cell-cycle transition.