| First Author | Dawar S | Year | 2017 |
| Journal | Oncogene | Volume | 36 |
| Issue | 19 | Pages | 2704-2714 |
| PubMed ID | 27991927 | Mgi Jnum | J:241310 |
| Mgi Id | MGI:5901787 | Doi | 10.1038/onc.2016.423 |
| Citation | Dawar S, et al. (2017) Caspase-2-mediated cell death is required for deleting aneuploid cells. Oncogene 36(19):2704-2714 |
| abstractText | 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. |
