# Role of Cyclin-Dependent Kinase 1 in Translational Regulation in the M-Phase
## 1 Introduction
### Global mRNA Translation during the M-Phase  
The dynamic control of mRNA translation has a significant impact on many intracellular processes. Translation of mRNA is regulated mostly during the initiation phase by initiation factors interacting with a specific structure bound to the 5'UTR of an mRNA molecule, the 5' cap (m7 GppN) [16; 17; 18; 19]. The cap structure is specifically recognized by the eukaryotic initiation factor complex (elf4F) comprised of the cap-binding eukaryotic translation initiation factor 4E (elF4E), the RNA helicase eIF4A and the scaffold protein eIF4G [20; 21]. EIF4G also binds the poly(A)-binding protein (PABP) [22], thereby enabling the circularization of the mRNA [23]. Suppression of cap-dependent translation coincides with eIF4E dephosphorylation (reviewed in [1]) and occurs together with an increased level of hypophosphorylated 4E-BP1 [24]. The phosphorylation status of 4E-BP1 depends on nutrients, extracellular signals and stress factors (reviewed in [25]) (Figure 3). Figure 2: Activated cyclin dependent kinase 1 (CDK1) supports mRNA translation during the M-phase. During the G2-phase, inactive CDK1 with minimal amount of regulatory cyclin B protein (CCNB) is present. Prior to nuclear envelope breakdown (NEBD) CCNB accumulates in the nucleus and binds to CDK1 resulting in an increase of CDK1 activity which leads to NEBD and localization of the complex at the newly forming spindle area. Post NEBD, active CDK1 influences translational reprogramming which contributes to successful M-phase progression. According to the published data, it is considered that global translation is substantially decreased during the M-phase (Figure 1) [26; 27; 28; 29]. Five decades ago a 50-70% reduction of global protein synthesis in synchronized mammalian cells undergoing mitosis was described [30; 31] and more recent data presented a 35% decrease in the translation rate during mitosis [29]. It has been documented that the intensity of protein synthesis suppression in cells undergoing mitosis is related to the method of cell synchronization [32; 33]. An objection has been raised that the data of downregulation of protein translation in mitotic cells were built on the effects of cellular stress associated with cell cycle synchronization protocol [34]. The reduction of global translation in cells undergoing cell division is believed to result from phosphorylation changes in translation initiation factors. The increased phosphorylation of an \(\alpha\) subunit of eukaryotic initiation factor 2\(\alpha\) (eIF2\(\alpha\)) induced in synchronized cells by cell cycle progression through the G2/M phase was determined as the cause of the downregulation of mRNA translation [35; 36]. An intense and long-term eIF2\(\alpha\) phosphorylation on Ser51 can suppress global translation and induce cell death [37; 38]. When the possible effect of synchronization on translation rates was eliminated, flow cytometry data revealed that there were no significant variations in global translation rates throughout the cell cycle [36]. In contrast to populations of nonsynchronized cells, the oocytes isolated from mammalian ovaries are arrested in the prophase of the first meiotic division and synchronously resume meiosis without chemical induction [39; 40]. In oocytes, global translation decreases during meiotic progression and postfertilization [41; 42]. Despite CDK1 activity in the M-phase leading to a significant reduction of global translation in mitosis [29] and meiosis [41; 42], a subset of mRNAs become translated during the M-phase progression which might be the result of CDK1 influencing the upregulation of the  
Figure 3: Positive and negative factors affecting eukaryotic translation initiation. (**A**) Inactivity of M phase-promoting factor (MPF) during interphase; lack of nutrients or stress lead to dephosphorylation of eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) which results in formation of translational repressor complex on mRNA.