CDK 磷酸化翻译起始因子将蛋白质翻译与细胞周期转变偶联。
CDK Phosphorylation of Translation Initiation Factors Couples Protein Translation with Cell-Cycle Transition.
机构信息
Department of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94143, USA.
出版信息
Cell Rep. 2018 Dec 11;25(11):3204-3214.e5. 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 mG 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.
真核生物中的蛋白质翻译与细胞周期有关，在细胞周期的 G1 期，翻译速率比有丝分裂期更为活跃。然而，基本的细胞周期调控机制是否在 G1/S 细胞周期转换期间直接激活蛋白质翻译仍不清楚。我们使用早期分化的真核生物布氏锥虫作为模型生物，报告称 G1 周期蛋白依赖性激酶 CRK1 磷酸化两个翻译起始因子 eIF4E4 和 PABP1，以促进 G1/S 细胞周期转换和全局蛋白质翻译。CRK1 对 eIF4E4 的磷酸化增强了与 mG 帽结构的结合以及与 eIF4E4 和 eIF4G3 的相互作用，而 CRK1 对 PABP1 的磷酸化促进了与 poly(A) 序列的结合、自身相互作用以及与 eIF4E4 的相互作用。这些发现表明，细胞周期蛋白依赖性激酶调节翻译起始因子将全局蛋白质翻译与 G1/S 细胞周期转换偶联。
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