Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/106125
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Type: Journal article
Title: Caspase-2-mediated cell death is required for deleting aneuploid cells
Author: Dawar, S.
Lim, Y.
Puccini, J.
White, M.
Thomas, P.
Bouchier-Hayes, L.
Green, D.
Dorstyn, L.
Kumar, S.
Citation: Oncogene, 2017; 36(19):2704-2714
Publisher: Nature Publishing Group
Issue Date: 2017
ISSN: 0950-9232
1476-5594
Statement of
Responsibility: 
S Dawar, Y Lim, J Puccini, M White, P Thomas, L Bouchier-Hayes, D R Green, L Dorstyn and S Kumar
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.
Keywords: Animals; Mice, Knockout; Humans; Mice; Aneuploidy; Chromosomal Instability; Apoptosis; Oxidative Stress; Caspase 2
Rights: Copyright © 2016, Rights Managed by Nature Publishing Group. This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/.
RMID: 0030063130
DOI: 10.1038/onc.2016.423
Grant ID: http://purl.org/au-research/grants/nhmrc/1043057
http://purl.org/au-research/grants/nhmrc/1103006
Appears in Collections:Medicine publications

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