Please use this identifier to cite or link to this item:
https://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/. |
DOI: | 10.1038/onc.2016.423 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1043057 http://purl.org/au-research/grants/nhmrc/1103006 |
Published version: | http://dx.doi.org/10.1038/onc.2016.423 |
Appears in Collections: | Aurora harvest 3 Medicine publications |
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hdl_106125.pdf | Published version | 1.56 MB | Adobe PDF | View/Open |
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