Journal
ONCOGENE
Volume 34, Issue 19, Pages 2483-2492Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2014.192
Keywords
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Funding
- National Institutes of Health PO1 grant [CA50661]
- National Institutes of Health RO1 grant [CA30002, CA34722]
- Ramalingaswami fellowship
- CREST fellowship
- Association for International Cancer Research
- Worldwide Cancer Research [11-0775] Funding Source: researchfish
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Polyoma small T antigen (PyST), an early gene product of the polyoma virus, has been shown to cause cell death in a number of mammalian cells in a protein phosphatase 2A (PP2A)-dependent manner. In the current study, using a cell line featuring regulated expression of PyST, we found that PyST arrests cells in mitosis. Live-cell and immunofluorescence studies showed that the majority of the PyST expressing cells were arrested in prometaphase with almost no cells progressing beyond metaphase. These cells exhibited defects in chromosomal congression, sister chromatid cohesion and spindle positioning, thereby resulting in the activation of the spindle assembly checkpoint. Prolonged mitotic arrest then led to cell death via mitotic catastrophe. Cell cycle inhibitors that block cells in G1/S prevented PyST-induced death. PyST-induced cell death that occurs during M is not dependent on p53 status. These data suggested, and our results confirmed, that PP2A inhibition could be used to preferentially kill cancer cells with p53 mutations that proliferate normally in the presence of cell cycle inhibitors.
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