# Role of Cyclin-Dependent Kinase 1 in Translational Regulation in the M-Phase
## 2 CDK1 Contributes to the Reprograming of Translation during M-Phase  
Ribosomes are considered as executors of the translational program through their role in mRNA decoding and protein synthesis. In eukaryotes, ribosome assembly is a complex process involving more than 200 assembly factors and takes place in the cytoplasm. The activity of CDK1 is coupled with NEBD (Figure 1) leading to the release of a number of nuclear factors which have either a positive or a negative role in the fate of the mRNA e.g., RNA binding proteins, rRNA, ncRNAs and mRNA. Thus CDK1, via nuclear factor release, has direct and indirect influences on translational reprogramming as the cell enters M-phase (reviewed in [45]). CDK1 regulates ribosome assembly by targeting specific ribosomal proteins. During the G2/M phase, CDK1 phosphorylates ribosomal protein S3 (RPS3), which is a multifunctional protein involved in translation, DNA repair and apoptosis. Phosphorylation of RPS3 by CDK1 is important for the nuclear accumulation of RPS3 [46]. RPS3 is localized evenly in the cytoplasm of germinal vesicle (GV) oocytes and with a higher concentration at the newly forming spindle in NEBD oocytes and mitotic cells [47; 48]. It was documented that CDK1 cosediments in the polysome fraction and mass spectrometry has revealed that CDK1 is associated with ribosomes [49]. This finding is in line with the notion that ribosomal protein L12 (RPL12) is a known substrate of CDK1 (Table 1) and RPL12 phosphorylation has been shown to enhance the mitotic translation program [50]. RPL12 has been reported to be phosphorylated on Ser38 in different species [57]. Phosphorylation of RPL12 regulates the translation of specific subsets of RNA during mitosis [50]. In HeLa cells, phosphorylation of RPL12 at Ser38 peaks in mitosis and reaches the lowest level during the S-phase [50; 58]. In eukaryotes, the sequence surrounding Ser38 is highly conserved and matches a consensus motif for CDK1 substrates [50]. Inhibition of CDK1 induced a progressive decrease in the percentage of heavy polysomes and a decline in polypeptide synthesis [13]. The nucleolus is a large nuclear organelle assembled around ribosomal genes (rDNAs) and is a site of ribosomal assembly. The assembly and disassembly of the nucleolus depends on the equilibrium between the phosphorylation/dephosphorylation of the transcription machinery \begin{table}
\begin{tabular}{c c c c} \hline \hline  & **CDK1 Substrate** & **Ref.** & **Role of CDK1 Substrate** \\ \hline \multirow{4}{*}{CDK1 and mTOR} & Raptor & [51] & mTOR phosphorylation and activation \\  & mTOR (Ser2448) & [7] & 4E-BP1 and p7056K phosphorylation \\  & p7056K & [8; 33] & Regulation of TOP mRNA translation \\  & LAR1 & [13; 52] & Regulation of TOP mRNA translation \\ \hline \multirow{4}{*}{CDK1 and 4E-BP1} & 4E-BP1 & [33] & Thr37/Thr46 phosphorylation primes 4E-BP1 for \\  & (Thr37/Thr46) & Ser65 and Thr70 phosphorylation \\ \cline{1-1}  & 4E-BP1 (Thr70) & [7; 8] & Thr70 phosphorylation regulates 4E-BP1 \\ \cline{1-1}  & 4E-BP1 (Ser83) & [8] & The role of Ser83 phosphorylation is unknown \\ \hline \multirow{4}{*}{CDK1 and ribo-some assembly} & eIF2A & [13] & Regulation of eIF2 complex \\ \cline{1-1}  & eIF4G1 & [53] & mRNA recruitment to the ribosome \\ \cline{1-1}  & RPL12 & [50] & Translational program \\ \hline \multirow{4}{*}{CDK1 and elongation} & eEF1B & [54] & Allows ribosome movement along RNA \\ \cline{1-1}  & eEF1D & [55] & Delivery of aminoacyl-tRNA to the ribosome \\ \cline{1-1}  & eEF2K & [56] & Regulation the elongation step of protein synthesis \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Known cyclin dependent kinase 1 (CDK1) substrates involved in translation. CDK1 controls the phosphorylation status and activity of proteins involved in the initiation (mammalian target of rapamycin (mTOR), eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1), ribosomal protein 56 kinase B1 (p7056K)) and elongation (eukaryotic elongation factor 2 kinase (eEF2K)) steps of mRNA translation.