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.

在有丝分裂过程中，大多数mRNA的翻译都受到强烈抑制。建议的几个解释性假设中没有一个可以完全解释这种现象的分子基础。在这里我们报告说，依赖细胞周期蛋白的CDK11 / p58（一种在M期大量表达的丝氨酸/苏氨酸激酶）通过磷酸化翻译因子eIF3复合物的亚基（eIF3F）来抑制总体翻译，这对于大多数mRNA的翻译起始是必不可少的。CDK11 / p58的异位表达强烈抑制帽依赖翻译，而CDK11 / p58的敲低则使M期的翻译抑制无效。我们确定了由CDK11 / p58引起M期特异性翻译抑制的eIF3F中的磷酸化位点。eIF3F中CDK11 / p58靶位点的丙氨酸替代作用使其对细胞周期依赖性翻译调节的影响无效。秀丽隐杆线虫对人类。