A cyclin-dependent kinase, CDK11/p58, represses cap-dependent translation during mitosis
Sihyeon An1, Oh Sung Kwon1, Jinbae Yu1
1PBC, Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Cheongam-ro 77, Nam-gu, Pohang-si, Gyeongsangbuk-do, 37673, Republic of Korea.
Abstract:
During mitosis, translation of most mRNAs is strongly repressed; none of the several explanatory hypotheses suggested can fully explain the molecular basis of this phenomenon. Here we report that cyclin-dependent CDK11/p58-a serine/threonine kinase abundantly expressed during M phase-represses overall translation by phosphorylating a subunit (eIF3F) of the translation factor eIF3 complex that is essential for translation initiation of most mRNAs. Ectopic expression of CDK11/p58 strongly repressed cap-dependent translation, and knockdown of CDK11/p58 nullified the translational repression during M phase. We identified the phosphorylation sites in eIF3F responsible for M phase-specific translational repression by CDK11/p58. Alanine substitutions of CDK11/p58 target sites in eIF3F nullified its effects on cell cycle-dependent translational regulation. The mechanism of translational regulation by the M phase-specific kinase, CDK11/p58, has deep evolutionary roots considering the conservation of CDK11 and its target sites on eIF3F from C. elegans to humans.
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