Abstract
Cyclin dependent kinase 1 (CDK1) has been primarily identified as a key cell cycle regulator in both mitosis and meiosis. Recently, an extramitotic function of CDK1 emerged when evidence was found that CDK1 is involved in many cellular events that are essential for cell proliferation and survival. In this review we summarize the involvement of CDK1 in the initiation and elongation steps of protein synthesis in the cell. During its activation, CDK1 influences the initiation of protein synthesis, promotes the activity of specific translational initiation factors and affects the functioning of a subset of elongation factors. Our review provides insights into gene expression regulation during the transcriptionally silent M-phase and describes quantitative and qualitative translational changes based on the extramitotic role of the cell cycle master regulator CDK1 to optimize temporal synthesis of proteins to sustain the division-related processes: mitosis and cytokinesis.
Highlights
Despite Cyclin Dependent Kinase 1 (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 mammalian target of rapamycin/4F axis [7,26,27,43,44]
The increased phosphorylation of an α subunit of eukaryotic initiation factor 2α phase, CDK1 phosphorylates ribosomal protein S3 (RPS3), which is a multifunctional protein induced in synchronized cells by cell cycle progression through the G2/M phase was determined involved in translation, DNA repair and apoptosis
Phosphorylation of the main mammalian target of rapamycin (mTOR) substrates, p70S6K and 4E (eIF4E)-binding protein 1 (4E-BP1), is dependent on CDK1 during mitosis [8,13,33] (Table 1) and CDK1 can substitute for mTOR kinase in the activation of cap-dependent translation in mitotic cells, suggesting that an alternate pathway for the regulation of cap-dependent translation exists [29,33]
Summary
Cyclin Dependent Kinase 1 (CDK1) Is a Subunit of the M Phase-Promoting Factor (MPF). CDK1 activity sharply increases at the beginning of the M-phase and is inactivated at the end [3,4,5]. 1. Dynamics of cyclin dependent (CDK1)activity, activity, global translation and inactivation. CDK1 activity peaks during assembly of the spindle and 4E-BP1 becomes exclusively (red arrowhead) which results in its inactivation as a translational repressor. CDK1 activity drops alongside the increased activity of the cap-dependent translational repressor 4E-BP1. At the exit of the M-phase, CDK1 activity drops alongside increased activity Immunoblot of the cap-dependent. The intensity of global translation decreases during course of using pan 4E-BP1 antibody shows an exclusive phosphorylation shift in the M-phasethe of time the mouse the M-phase. Shift in the M-phase of the mouse oocyte (red arrowhead) [7]
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