Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/106125
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dc.contributor.author | Dawar, S. | - |
dc.contributor.author | Lim, Y. | - |
dc.contributor.author | Puccini, J. | - |
dc.contributor.author | White, M. | - |
dc.contributor.author | Thomas, P. | - |
dc.contributor.author | Bouchier-Hayes, L. | - |
dc.contributor.author | Green, D. | - |
dc.contributor.author | Dorstyn, L. | - |
dc.contributor.author | Kumar, S. | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | Oncogene, 2017; 36(19):2704-2714 | - |
dc.identifier.issn | 0950-9232 | - |
dc.identifier.issn | 1476-5594 | - |
dc.identifier.uri | http://hdl.handle.net/2440/106125 | - |
dc.description.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. | - |
dc.description.statementofresponsibility | S Dawar, Y Lim, J Puccini, M White, P Thomas, L Bouchier-Hayes, D R Green, L Dorstyn and S Kumar | - |
dc.language.iso | en | - |
dc.publisher | Nature Publishing Group | - |
dc.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/. | - |
dc.source.uri | http://dx.doi.org/10.1038/onc.2016.423 | - |
dc.subject | Animals | - |
dc.subject | Mice, Knockout | - |
dc.subject | Humans | - |
dc.subject | Mice | - |
dc.subject | Aneuploidy | - |
dc.subject | Chromosomal Instability | - |
dc.subject | Apoptosis | - |
dc.subject | Oxidative Stress | - |
dc.subject | Caspase 2 | - |
dc.title | Caspase-2-mediated cell death is required for deleting aneuploid cells | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1038/onc.2016.423 | - |
dc.relation.grant | http://purl.org/au-research/grants/nhmrc/1043057 | - |
dc.relation.grant | http://purl.org/au-research/grants/nhmrc/1103006 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Kumar, S. [0000-0001-7126-9814] | - |
Appears in Collections: | Aurora harvest 3 Medicine publications |
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File | Description | Size | Format | |
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hdl_106125.pdf | Published version | 1.56 MB | Adobe PDF | View/Open |
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