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Caspase-2 is required for cell death induced by cytoskeletal disruption

Oncogene volume 27, pages 3393–3404 (2008)Cite this article

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.

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Abbreviations

Casp2:

caspase-2

cyto D:

cytochalasin D

KO:

knockout

MEFs:

mouse embryonic fibroblasts

MOMP:

mitochondrial outer membrane permeabilization

Pacl:

paclitaxel

Vinc:

vincristine

ZA:

zoledronic acid

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Acknowledgements

This work was supported by the National Health and Medical Research Council of Australia and the Cancer Council of South Australia. LD is a Royal Adelaide Hospital Florey Research Fellow.

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Authors and Affiliations

  1. Division of Haematology, Hanson Institute, IMVS, Adelaide, Australia

    L H Ho, S H Read, L Dorstyn, L Lambrusco & S Kumar

  2. Department of Medicine, Adelaide University, Adelaide, Australia

    S Kumar

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  1. L H Ho
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  2. S H Read
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  3. L Dorstyn
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  4. L Lambrusco
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  5. S Kumar
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Correspondence to S Kumar.

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Ho, L., Read, S., Dorstyn, L. et al. Caspase-2 is required for cell death induced by cytoskeletal disruption. Oncogene 27, 3393–3404 (2008). https://doi.org/10.1038/sj.onc.1211005

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