ArticleProceedings of the National Academy of Sciences of the United States of America2010
Loss of human Greatwall results in G2 arrest and multiple mitotic defects due to deregulation of the cyclin B-Cdc2/PP2A balance.
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 424 papers.
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424 citing papers in PubMed, 689 citations in OpenAlex.
- Greatwall kinase regulates acute myeloid leukaemia cell division through a non-canonical mechanism.EMBO reports · 2026Article
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- Molecular basis for the activation of Aurora A and Plk1 kinases during mitotic entry.The EMBO journal · 2026Article
- MASTL Promotes Hepatocellular Carcinoma Progression and Paclitaxel Resistance Through Mitotic Catastrophe.Cancer science · 2026Article
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- A mechanism for the disrupted redox regulation of vascular contractility during aging.iScience · 2026Article
- Targeting PP2A in cancer: an underrated option.Journal of experimental & clinical cancer research : CR · 2025Review
- Hydrogen Gas Mitigates Acute Hypoxia-Induced Oxidative and Inflammatory Brain Injuries in Medaka (Antioxidants (Basel, Switzerland) · 2025Article
- The balance between B55α and Greatwall expression levels predicts sensitivity to Greatwall inhibition in cancer cells.Nature communications · 2025Article
- Comparative Analysis of Davidson and Glyoxal Fixatives on Autofluorescence and Immunolabeling in Medaka (Biomedicines · 2025Article
- Targeting receptor for activated C kinase 1 with a small molecule induces mitotic catastrophe and suppresses lipid metabolic reprogramming in hepatocellular carcinoma.Clinical and translational medicine · 2025Article
- Examining the vulnerability of adult neuron subtypes to tau-mediated toxicity in Drosophila.Translational psychiatry · 2025Article
- PP2A-B56 regulates Mid1 protein levels for proper cytokinesis in fission yeast.Molecular biology of the cell · 2025Article
- Protein serine/threonine phosphatases in tumor microenvironment: a vital player and a promising therapeutic target.Theranostics · 2025Review
- AoRan1 Is Involved in Regulating Conidiation, Stress Resistance, Secondary Metabolism, and Pathogenicity inMicroorganisms · 2024Article
- MiR-425-5p suppression of Crebzf regulates oocyte aging via chromatin modification.GeroScience · 2024Article
- IL-22 regulates MASTL expression in intestinal epithelial cells.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
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- Greatwall-Endos-PP2A/B55Open biology · 2024Article
- Distinct roles of the left and right prelimbic cortices in the modulation of ethanol consumption in male mice under acute and chronic social defeat stress.Psychopharmacology · 2024Article
364 more citing papers are in PubMed but not listed here.
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6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Here we show that the functional human ortholog of Greatwall protein kinase (Gwl) is the microtubule-associated serine/threonine kinase-like protein, MAST-L. This kinase promotes mitotic entry and maintenance in human cells by inhibiting protein phosphatase 2A (PP2A), a phosphatase that dephosphorylates cyclin B-Cdc2 substrates. The complete depletion of Gwl by siRNA arrests human cells in G2. When the levels of this kinase are only partially depleted, however, cells enter into mitosis with multiple defects and fail to inactivate the spindle assembly checkpoint (SAC). The ability of cells to remain arrested in mitosis by the SAC appears to be directly proportional to the amount of Gwl remaining. Thus, when Gwl is only slightly reduced, cells arrest at prometaphase. More complete depletion correlates with the premature dephosphorylation of cyclin B-Cdc2 substrates, inactivation of the SAC, and subsequent exit from mitosis with severe cytokinesis defects. These phenotypes appear to be mediated by PP2A, as they could be rescued by either a double Gwl/PP2A knockdown or by the inhibition of this phosphatase with okadaic acid. These results suggest that the balance between cyclin B-Cdc2 and PP2A must be tightly regulated for correct mitotic entry and exit and that Gwl is crucial for mediating this regulation in somatic human cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.