Functional Activation of Nedd2/ICH-1 (Caspase-2) Is an Early Process in Apoptosis*
- From the Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Rundle Mall, Adelaide, SA 5000, Australia
Abstract
The ICE/CED-3 family of proteases (caspases) play a central role in the execution phase of apoptosis. These proteases are synthesised as precursor molecules that require processing at specific aspartate residues to produce the two subunits that comprise the active enzyme. The activation of some of these proteases has been shown to occur during apoptosis. Here we show that Nedd2/ICH-1 (caspase-2) is activated during apoptosis induced by a variety of apoptotic stimuli. This activation occurs very early upon treatment of cells with apoptotic agents and appears to precede the activation of CPP32 (caspase-3). The activation of Nedd2 was not seen in cells that are resistant to apoptosis. These observations suggest that Nedd2 is an early effector in the pathway leading to cell death. Our observations also lend weight to the hypothesis that a group of caspases containing long prodomains are the first to be activated in response to apoptotic signals and that they lie upstream of a second class of caspases such as CPP32 containing short or no prodomains.
Footnotes
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↵* This work was supported by a Wellcome Trust Senior Research Fellowship in Medical Science and Grant 960532 from the National Health and Medical Research Council of Australia (to S. K.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ To whom correspondence should be addressed: Hanson Centre for Cancer Research, Inst. of Medical and Veterinary Science, P.O. Box 14, Rundle Mall, Adelaide, SA 5000, Australia. Tel.: 61-8-8222-3738; Fax: 61-8-8222-3139; E-mail: skumar{at}immuno.imvs.sa.gov.au.
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↵1 The abbreviations used are: ICE, interleukin-1β-converting enzyme; TNF, tumor necrosis factor; IL, interleukin; PIPES, 1,4-piperazinediethanesulfonic acid; CHAPS, 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid; Gy, gray; PARP, poly(ADP-ribose)polymerase.
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↵2 N. L. Harvey and S. Kumar, unpublished observations.
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- Received February 20, 1997.
