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- Title
Caspase-2 is required for cell death induced by cytoskeletal disruption.
- Authors
Ho, L. H.; Read, S. H.; Dorstyn, L.; Lambrusco, L.; Kumar, S.
- Abstract
Caspase-2 is one of the most conserved caspases, yet its biological function remains a matter of controversy. In the present article we analysed mouse embryonic fibroblasts (MEFs) from caspase-2 knockout mice for their sensitivity to various apoptosis inducing agents. We found that cell death induced by drugs that disrupt cytoskeleton is significantly inhibited in Casp2−/− MEFs. These drugs included zoledronic acid, vincristine, cytochalasin D and paclitaxel. We demonstrate that MEFs lacking Casp2 show clonogenic survival following drug treatment, whereas all Casp2+/+ MEFs die, indicating that caspase-2 is required for apoptosis induced by cytoskeletal disruption. We further found that caspase-2 mediates apoptosis via Piddosome, Bid and Bax activation, and cytochrome c release. In the absence of caspase-2, Bid and Bax activation, and cytochrome c release are significantly delayed following drug treatment. Our data provide strong support for a context-dependent function of caspase-2 in apoptosis.Oncogene (2008) 27, 3393–3404; doi:10.1038/sj.onc.1211005; published online 14 January 2008
- Subjects
CELL death; CYTOSKELETON; APOPTOSIS; CYTOCHROME c; CONNECTIVE tissue cells; VINCAMINE; PACLITAXEL; ANTINEOPLASTIC agents
- Publication
Oncogene, 2008, Vol 27, Issue 24, p3393
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1211005