ArticleScientific reports2015
The lethal response to Cdk1 inhibition depends on sister chromatid alignment errors generated by KIF4 and isoform 1 of PRC1.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- The mitotic ATR-Chk1 pathway promotes CDK1 activity for faithful chromosome segregation.Cell reports · 2025Article
- Controlled Exit from the G2/M Checkpoint in RPE-1 Cells Using RO3306: Enrichment of Phase-Specific Cell Populations for In-Depth Analyses of Mitotic Events.International journal of molecular sciences · 2025Article
- Reversible and effective cell cycle synchronization method for studying stage-specific processes.Life science alliance · 2025Article
- Exploring the role of cell cycle regulation in human mature adipocyte dedifferentiation.Frontiers in cell and developmental biology · 2025Article
- Elraglusib Induces Cytotoxicity via Direct Microtubule Destabilization Independently of GSK3 Inhibition.Cancer research communications · 2024Article
- Reversible and effective cell cycle synchronization method for studying stage-specific investigations.bioRxiv : the preprint server for biology · 2024Article
- Non-centrosomal microtubules at kinetochores promote rapid chromosome biorientation during mitosis in human cells.Current biology : CB · 2022Article
- The Renaissance of Cyclin Dependent Kinase Inhibitors.Cancers · 2022Review
- Identification of a novel nucleolar protein complex required for mitotic chromosome segregation through centromeric accumulation of Aurora B.Nucleic acids research · 2020Article
- Cyclin A triggers Mitosis either via the Greatwall kinase pathway or Cyclin B.The EMBO journal · 2020Article
- High-resolution imaging reveals how the spindle midzone impacts chromosome movement.The Journal of cell biology · 2019Article
- Targeting the cell cycle in head and neck cancer by Chk1 inhibition: a novel concept of bimodal cell death.Oncogenesis · 2019Article
- Phosphoregulation of the oncogenic protein regulator of cytokinesis 1 (PRC1) by the atypical CDK16/CCNY complex.Experimental & molecular medicine · 2019Article
- Article
- GTSE1 regulates spindle microtubule dynamics to control Aurora B kinase and Kif4A chromokinesin on chromosome arms.The Journal of cell biology · 2017Article
- Kif4 Is Essential for Mouse Oocyte Meiosis.PloS one · 2017Article
- A generic strategy for CRISPR-Cas9-mediated gene tagging.Nature communications · 2015Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclin-dependent kinase 1 (Cdk1) is absolutely essential for cell division. Complete ablation of Cdk1 precludes the entry of G2 phase cells into mitosis, and is early embryonic lethal in mice. Dampening Cdk1 activation, by reducing gene expression or upon treatment with cell-permeable Cdk1 inhibitors, is also detrimental for proliferating cells, but has been associated with defects in mitotic progression, and the formation of aneuploid daughter cells. Here, we used a large-scale RNAi screen to identify the human genes that critically determine the cellular toxicity of Cdk1 inhibition. We show that Cdk1 inhibition leads to fatal sister chromatid alignment errors and mitotic arrest in the spindle checkpoint. These problems start early in mitosis and are alleviated by depletion of isoform 1 of PRC1 (PRC1-1), by gene ablation of its binding partner KIF4, or by abrogation of KIF4 motor activity. Our results show that, normally, Cdk1 activity must rise above the level required for mitotic entry. This prevents KIF4-dependent PRC1-1 translocation to astral microtubule tips and safeguards proper chromosome congression. We conclude that cell death in response to Cdk1 inhibitors directly relates to chromosome alignment defects generated by insufficient repression of PRC1-1 and KIF4 during prometaphase.
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