ArticleProceedings of the National Academy of Sciences of the United States of America2010
Cell division cycle 6, a mitotic substrate of polo-like kinase 1, regulates chromosomal segregation mediated by cyclin-dependent kinase 1 and separase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 46 citations in OpenAlex.
- Interaction between CDC6 and Tmod3 accelerates resistance to paclitaxel through focal adhesion assembly.Signal transduction and targeted therapy · 2025Article
- 14-3-3ε inhibits premature centriole disengagement by inhibiting the activity of Plk1 and separase.Journal of cell science · 2025Article
- CDC6 Inhibits CDK1 Activity in MII-Arrested Oocyte Cell-Free Extract.International journal of molecular sciences · 2025Article
- CDC6 as a Key Inhibitory Regulator of CDK1 Activation Dynamics and the Timing of Mitotic Entry and Progression.Biology · 2023Review
- Targeting CDK1 in cancer: mechanisms and implications.NPJ precision oncology · 2023Review
- On the assembly of the mitotic spindle, bistability and hysteresis.Cellular and molecular life sciences : CMLS · 2023Article
- PLK1-mediated phosphorylation of β-catenin enhances its stability and transcriptional activity for extracellular matrix remodeling in metastatic NSCLC.Theranostics · 2023Article
- Differential condensation of sister chromatids acts with Cdc6 to ensure asynchronous S-phase entry in Drosophila male germline stem cell lineage.Developmental cell · 2022Article
- DNA Replication Licensing Factors: Novel Targets for Cancer Therapy via Inhibiting the Stemness of Cancer Cells.International journal of biological sciences · 2022Review
- Cell-cycle phospho-regulation of the kinetochore.Current genetics · 2021Review
- Cell cycle and complement inhibitors may be specific for treatment of spinal cord injury in aged and young mice: Transcriptomic analyses.Neural regeneration research · 2018Article
- Nuclear pore protein NUP88 activates anaphase-promoting complex to promote aneuploidy.The Journal of clinical investigation · 2016Article
- Cell Division Cycle 6 Promotes Mitotic Slippage and Contributes to Drug Resistance in Paclitaxel-Treated Cancer Cells.PloS one · 2016Article
- Control of myogenesis by rodent SINE-containing lncRNAs.Genes & development · 2013Article
- Cdc6 is required for meiotic spindle assembly in Xenopus oocytes.Cell cycle (Georgetown, Tex.) · 2012Article
- Phosphorylation of MCM3 protein by cyclin E/cyclin-dependent kinase 2 (Cdk2) regulates its function in cell cycle.The Journal of biological chemistry · 2011Article
- Dronc caspase exerts a non-apoptotic function to restrain phospho-Numb-induced ectopic neuroblast formation in Drosophila.Development (Cambridge, England) · 2011Article
- Regulation of the final stage of mitosis by components of the pre-replicative complex and a polo kinase.Cell cycle (Georgetown, Tex.) · 2011Article
- Canonical and Alternative Pathways in Cyclin-Dependent Kinase 1/Cyclin B Inactivation upon M-Phase Exit in Xenopus laevis Cell-Free Extracts.Enzyme research · 2011Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Defining the links between cell division and DNA replication is essential for understanding normal cell cycle progression and tumorigenesis. In this report we explore the effect of phosphorylation of cell division cycle 6 (Cdc6), a DNA replication initiation factor, by polo-like kinase 1 (Plk1) on the regulation of chromosomal segregation. In mitosis, the phosphorylation of Cdc6 was highly increased, in correlation with the level of Plk1, and conversely, Cdc6 is hypophosphorylated in Plk1-depleted cells, although cyclin A- and cyclin B1-dependent kinases are active. Binding between Cdc6 and Plk1 occurs through the polo-box domain of Plk1, and Cdc6 is phosphorylated by Plk1 on T37. Immunohistochemistry studies reveal that Cdc6 and Plk1 colocalize to the central spindle in anaphase. Expression of T37V mutant of Cdc6 (Cdc6-TV) induces binucleated cells and incompletely separated nuclei. Wild-type Cdc6 but not Cdc6-TV binds cyclin-dependent kinase 1 (Cdk1). Expression of wild-type Plk1 but not kinase-defective mutant promotes the binding of Cdc6 to Cdk1. Cells expressing wild-type Cdc6 display lower Cdk1 activity and higher separase activity than cells expressing Cdc6-TV. These results suggest that Plk1-mediated phosphorylation of Cdc6 promotes the interaction of Cdc6 and Cdk1, leading to the attenuation of Cdk1 activity, release of separase, and subsequent anaphase progression.
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