Polyoma small T antigen triggers cell death via mitotic catastrophe.

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, 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.

journal_name

Oncogene

journal_title

Oncogene

authors

Pores Fernando AT,Andrabi S,Cizmecioglu O,Zhu C,Livingston DM,Higgins JM,Schaffhausen BS,Roberts TM

doi

10.1038/onc.2014.192

subject

Has Abstract

pub_date

2015-05-07 00:00:00

pages

2483-92

issue

19

eissn

0950-9232

issn

1476-5594

pii

onc2014192

journal_volume

34

pub_type

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