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Caspase-2-mediated cell death is required for deleting aneuploid cells.

ABSTRACT: Caspase-2, one of the most evolutionarily conserved of the caspase family, has been implicated in maintenance of chromosomal stability and tumour suppression. Caspase-2 deficient (Casp2-/-) mice develop normally but show premature ageing-related traits and when challenged by certain stressors, succumb to enhanced tumour development and aneuploidy. To test how caspase-2 protects against chromosomal instability, we utilized an ex vivo system for aneuploidy where primary splenocytes from Casp2-/- mice were exposed to anti-mitotic drugs and followed up by live cell imaging. Our data show that caspase-2 is required for deleting mitotically aberrant cells. Acute silencing of caspase-2 in cultured human cells recapitulated these results. We further generated Casp2C320S mutant mice to demonstrate that caspase-2 catalytic activity is essential for its function in limiting aneuploidy. Our results provide direct evidence that the apoptotic activity of caspase-2 is necessary for deleting cells with mitotic aberrations to limit aneuploidy.

SUBMITTER: Dawar S 

PROVIDER: S-EPMC5442422 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Caspase-2-mediated cell death is required for deleting aneuploid cells.

Dawar S S   Lim Y Y   Puccini J J   White M M   Thomas P P   Bouchier-Hayes L L   Green D R DR   Dorstyn L L   Kumar S S  

Oncogene 20161219 19

Caspase-2, one of the most evolutionarily conserved of the caspase family, has been implicated in maintenance of chromosomal stability and tumour suppression. Caspase-2 deficient (Casp2<sup>-/-</sup>) mice develop normally but show premature ageing-related traits and when challenged by certain stressors, succumb to enhanced tumour development and aneuploidy. To test how caspase-2 protects against chromosomal instability, we utilized an ex vivo system for aneuploidy where primary splenocytes from  ...[more]

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