ArticleMolecular biology of the cell2005
Aurora kinase inhibitor ZM447439 blocks chromosome-induced spindle assembly, the completion of chromosome condensation, and the establishment of the spindle integrity checkpoint in Xenopus egg extracts.
Article in Molecular biology of the cell, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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54 citing papers in PubMed, 129 citations in OpenAlex.
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- Cytoskeletal polarization and cytokinetic signaling drives polar lobe formation in spiralian embryos.Developmental biology · 2019Article
- Dissecting the mechanisms of cell division.The Journal of biological chemistry · 2019Review
- CDK phosphorylation ofThe EMBO journal · 2019Article
- G2/M inhibitors as pharmacotherapeutic opportunities for glioblastoma: the old, the new, and the future.Cancer biology & medicine · 2018Article
- Dual recognition of chromatin and microtubules by INCENP is important for mitotic progression.The Journal of cell biology · 2017Article
- Transcriptome analysis of tetraploid cells identifies cyclin D2 as a facilitator of adaptation to genome doubling in the presence of p53.Molecular biology of the cell · 2016Article
- Combination of Eribulin and Aurora A Inhibitor MLN8237 Prevents Metastatic Colonization and Induces Cytotoxic Autophagy in Breast Cancer.Molecular cancer therapeutics · 2016Article
- Mitotic noncoding RNA processing promotes kinetochore and spindle assembly in Xenopus.The Journal of cell biology · 2016Article
- AMG 900, a potent inhibitor of aurora kinases causes pharmacodynamic changes in p-Histone H3 immunoreactivity in human tumor xenografts and proliferating mouse tissues.Journal of translational medicine · 2014Article
- cPKC regulates interphase nuclear size during Xenopus development.The Journal of cell biology · 2014Article
- Phosphorylation of myosin II-interacting guanine nucleotide exchange factor (MyoGEF) at threonine 544 by aurora B kinase promotes the binding of polo-like kinase 1 to MyoGEF.The Journal of biological chemistry · 2014Article
- Skp-cullin-F box E3 ligase component FBXL2 ubiquitinates Aurora B to inhibit tumorigenesis.Cell death & disease · 2013Article
- Calmodulin protects Aurora B on the midbody to regulate the fidelity of cytokinesis.Cell cycle (Georgetown, Tex.) · 2013Article
- A synergetic screening approach with companion effector for combination therapy: application to retinoblastoma.PloS one · 2013Article
- Tripolin A, a novel small-molecule inhibitor of aurora A kinase, reveals new regulation of HURP's distribution on microtubules.PloS one · 2013Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The Aurora family kinases contribute to accurate progression through several mitotic events. ZM447439 ("ZM"), the first Aurora family kinase inhibitor to be developed and characterized, was previously found to interfere with the mitotic spindle integrity checkpoint and chromosome segregation. Here, we have used extracts of Xenopus eggs, which normally proceed through the early embryonic cell cycles in the absence of functional checkpoints, to distinguish between ZM's effects on the basic cell cycle machinery and its effects on checkpoints. ZM clearly had no effect on either the kinetics or amplitude in the oscillations of activity of several key cell cycle regulators. It did, however, have striking effects on chromosome morphology. In the presence of ZM, chromosome condensation began on schedule but then failed to progress properly; instead, the chromosomes underwent premature decondensation during mid-mitosis. ZM strongly interfered with mitotic spindle assembly by inhibiting the formation of microtubules that are nucleated/stabilized by chromatin. By contrast, ZM had little effect on the assembly of microtubules by centrosomes at the spindle poles. Finally, under conditions where the spindle integrity checkpoint was experimentally induced, ZM blocked the establishment, but not the maintenance, of the checkpoint, at a point upstream of the checkpoint protein Mad2. These results show that Aurora kinase activity is required to ensure the maintenance of condensed chromosomes, the generation of chromosome-induced spindle microtubules, and activation of the spindle integrity checkpoint.
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