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

被引：100

作者：

Ho, L. H. ^{[1
]}

Read, S. H. ^{[1
]}

Dorstyn, L. ^{[1
]}

Lambrusco, L. ^{[1
]}

Kumar, S. ^{[1
,2
]}

机构：

[1] Inst Med & Vet Sci, Div Haematol, Hanson Inst, Adelaide, SA 5000, Australia

[2] Univ Adelaide, Dept Med, Adelaide, SA 5001, Australia

来源：

ONCOGENE | 2008年 / 27卷 / 24期

基金：

英国医学研究理事会;

关键词：

apoptosis; caspase-2; activation; Bid; Bax; initiator caspase; cytoskeleton;

D O I：

10.1038/sj.onc.1211005

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：3393 / 3404

页数：12

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