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Type: Journal article
Title: Capase-2 is required for cell death induced by cytoskeletal disruption
Author: Ho, L.
Read, S.
Dorstyn, L.
Lambrusco, L.
Kumar, S.
Citation: Oncogene, 2008; 27(24):3393-3404
Publisher: Nature Publishing Group
Issue Date: 2008
ISSN: 0950-9232
Statement of
L H Ho, S H Read, L Dorstyn, L Lambrusco and S Kumar.
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.
Keywords: apoptosis; caspase-2 activation; Bid; Bax; initiator caspase; cytoskeleton
RMID: 0020084853
DOI: 10.1038/sj.onc.1211005
Appears in Collections:Medicine publications

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