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

S. Dawar, Y. Lim, J. Puccini, M. White, Paul Thomas, L. Bouchier-Hayes, D. R. Green, L. Dorstyn, S. Kumar

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26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2704-2714
Number of pages11
JournalOncogene
Volume36
Issue number19
DOIs
Publication statusPublished - 11 May 2017
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Dawar, S., Lim, Y., Puccini, J., White, M., Thomas, P., Bouchier-Hayes, L., ... Kumar, S. (2017). Caspase-2-mediated cell death is required for deleting aneuploid cells. Oncogene, 36(19), 2704-2714. https://doi.org/10.1038/onc.2016.423