Polyoma small T antigen triggers cell death via mitotic catastrophe

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Polyoma small T antigen triggers cell death via mitotic catastrophe

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Title: Polyoma small T antigen triggers cell death via mitotic catastrophe
Author: Fernando, Arun T Pores; Andrabi, Shaida; Cizmecioglu, Onur; Zhu, Cailei; Livingston, David M.; Higgins, Jonathan M.G; Schaffhausen, Brian S; Roberts, Thomas M

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Citation: Fernando, Arun T Pores, Shaida Andrabi, Onur Cizmecioglu, Cailei Zhu, David M. Livingston, Jonathan M.G Higgins, Brian S Schaffhausen, and Thomas M Roberts. 2014. “Polyoma small T antigen triggers cell death via mitotic catastrophe.” Oncogene 34 (19): 2483-2492. doi:10.1038/onc.2014.192. http://dx.doi.org/10.1038/onc.2014.192.
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Abstract: 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, resulting in the activation of the Spindle Assembly Checkpoint (SAC). 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.
Published Version: doi:10.1038/onc.2014.192
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286542/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:23845192
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