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

Oncogene. 2017 May 11;36(19):2704-2714. doi: 10.1038/onc.2016.423. Epub 2016 Dec 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneuploidy*
  • Animals
  • Apoptosis / genetics*
  • Caspase 2 / genetics*
  • Caspase 2 / metabolism
  • Chromosomal Instability / genetics*
  • Humans
  • Mice
  • Mice, Knockout
  • Oxidative Stress / genetics

Substances

  • Caspase 2