Cells are equipped with a diverse network of signaling and regulatory proteins that function as cell cycle regulators and checkpoint proteins to ensure the proper progression of cell division. A key regulator of cell division is polo-like kinase 1 (PLK1), a member of the serine/threonine kinase family that plays an important role in regulating the mitotic and meiotic cell cycle. The phosphorylation of specific substrates mediated by PLK1 controls nuclear envelope breakdown (NEBD), centrosome maturation, proper spindle assembly, chromosome segregation, and cytokinesis. In mammalian oogenesis, PLK1 is essential for resuming meiosis before ovulation and for establishing the meiotic spindle. Among other potential roles, PLK1 regulates the localized translation of spindle-enriched mRNAs by phosphorylating and thereby inhibiting the translational repressor 4E-BP1, a downstream target of the mTOR (mammalian target of rapamycin) pathway. In this review, we summarize the functions of PLK1 in mitosis, meiosis, and cytokinesis and focus on the role of PLK1 in regulating mRNA translation. However, knowledge of the role of PLK1 in the regulation of meiosis remains limited.

• Keywords
• PLK1, mRNA translation, meiosis, mitosis, oocytes, polo-like kinase 1, spindle,
• MeSH
• Humans MeSH
• Meiosis MeSH
• Mitosis MeSH
• Polo-Like Kinase 1 MeSH
• Protein Serine-Threonine Kinases * metabolism   MeSH
• Cell Cycle Proteins * metabolism   MeSH
• Proto-Oncogene Proteins metabolism   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Protein Serine-Threonine Kinases * MeSH
• Cell Cycle Proteins * MeSH
• Proto-Oncogene Proteins MeSH

Cyclin A2 is a key regulator of the cell cycle, implicated both in DNA replication and mitotic entry. Cyclin A2 participates in feedback loops that activate mitotic kinases in G2 phase, but why active Cyclin A2-CDK2 during the S phase does not trigger mitotic kinase activation remains unclear. Here, we describe a change in localisation of Cyclin A2 from being only nuclear to both nuclear and cytoplasmic at the S/G2 border. We find that Cyclin A2-CDK2 can activate the mitotic kinase PLK1 through phosphorylation of Bora, and that only cytoplasmic Cyclin A2 interacts with Bora and PLK1. Expression of predominately cytoplasmic Cyclin A2 or phospho-mimicking PLK1 T210D can partially rescue a G2 arrest caused by Cyclin A2 depletion. Cytoplasmic presence of Cyclin A2 is restricted by p21, in particular after DNA damage. Cyclin A2 chromatin association during DNA replication and additional mechanisms contribute to Cyclin A2 localisation change in the G2 phase. We find no evidence that such mechanisms involve G2 feedback loops and suggest that cytoplasmic appearance of Cyclin A2 at the S/G2 transition functions as a trigger for mitotic kinase activation.

• MeSH
• Enzyme Activation genetics   MeSH
• Cell Nucleus metabolism   MeSH
• Chromatin metabolism   MeSH
• Cyclin A2 genetics   metabolism   MeSH
• Cyclin-Dependent Kinase 2 deficiency   genetics   MeSH
• Cytoplasm metabolism   MeSH
• Phosphorylation genetics   MeSH
• G2 Phase genetics   MeSH
• HeLa Cells MeSH
• Humans MeSH
• Mitosis genetics   MeSH
• Polo-Like Kinase 1 MeSH
• DNA Damage genetics   MeSH
• Protein Serine-Threonine Kinases metabolism   MeSH
• CDC2 Protein Kinase deficiency   genetics   MeSH
• Cell Cycle Proteins metabolism   MeSH
• Proto-Oncogene Proteins metabolism   MeSH
• S Phase genetics   MeSH
• Signal Transduction genetics   MeSH
• Transfection MeSH
• Protein Binding MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• bora protein, human MeSH Browser
• CCNA2 protein, human MeSH Browser
• CDK1 protein, human MeSH Browser
• CDK2 protein, human MeSH Browser
• Chromatin MeSH
• Cyclin A2 MeSH
• Cyclin-Dependent Kinase 2 MeSH
• Protein Serine-Threonine Kinases MeSH
• CDC2 Protein Kinase MeSH
• Cell Cycle Proteins MeSH
• Proto-Oncogene Proteins MeSH