Apoptotic cell death is of central importance in the pathogenesis of viral infections. Activation of a cascade of cysteine proteases, i.e. caspases, plays a key role in the effector phase of virus-induced apoptosis. However, little is known about pathways leading to the activation of initiator caspases in virus-infected host cells. Recently, we have shown that Sendai virus (SeV) infection triggers apoptotic cell death by activation of the effector caspase-3 and initiator caspase-8. We now investigated mechanisms leading to the activation of another initiator caspase, caspase-9. Unexpectedly we found that caspase-9 cleavage is not dependent on the presence of active caspases-3 or -8. Furthermore, the presence of caspase-9 in mouse embryonic fibroblast (MEF) cells was a prerequisite for Sendai virus-induced apoptotic cell death. Caspase-9 activation occurred without the release of cytochrome c from mitochondria and was not dependent on the presence of Apaf-1 or reactive oxygen intermediates. Our results therefore suggest an alternative mechanism for caspase-9 activation in virally infected cells beside the well characterized pathways via death receptors or mitochondrial cytochrome c release.

Bitzer, M., Armeanu, S., Prinz, F., Ungerechts, G., Wybranietz, W., Spiegel, M., et al. (2002). Caspase-8 and Apaf-1-independent caspase-9 activation in Sendai virus-infected cells. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 277(33), 29817-29824 [10.1074/jbc.M111898200].

Caspase-8 and Apaf-1-independent caspase-9 activation in Sendai virus-infected cells

CECCONI, FRANCESCO;
2002-01-01

Abstract

Apoptotic cell death is of central importance in the pathogenesis of viral infections. Activation of a cascade of cysteine proteases, i.e. caspases, plays a key role in the effector phase of virus-induced apoptosis. However, little is known about pathways leading to the activation of initiator caspases in virus-infected host cells. Recently, we have shown that Sendai virus (SeV) infection triggers apoptotic cell death by activation of the effector caspase-3 and initiator caspase-8. We now investigated mechanisms leading to the activation of another initiator caspase, caspase-9. Unexpectedly we found that caspase-9 cleavage is not dependent on the presence of active caspases-3 or -8. Furthermore, the presence of caspase-9 in mouse embryonic fibroblast (MEF) cells was a prerequisite for Sendai virus-induced apoptotic cell death. Caspase-9 activation occurred without the release of cytochrome c from mitochondria and was not dependent on the presence of Apaf-1 or reactive oxygen intermediates. Our results therefore suggest an alternative mechanism for caspase-9 activation in virally infected cells beside the well characterized pathways via death receptors or mitochondrial cytochrome c release.
2002
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/06 - ANATOMIA COMPARATA E CITOLOGIA
English
Con Impact Factor ISI
CYTOCHROME-C RELEASE; INDUCED APOPTOSIS; DEATH RECEPTORS; BCL-X; MITOCHONDRIA; PROCASPASE-9; CLEAVAGE; PATHWAYS; BINDING; APAF-1
8
Bitzer, M., Armeanu, S., Prinz, F., Ungerechts, G., Wybranietz, W., Spiegel, M., et al. (2002). Caspase-8 and Apaf-1-independent caspase-9 activation in Sendai virus-infected cells. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 277(33), 29817-29824 [10.1074/jbc.M111898200].
Bitzer, M; Armeanu, S; Prinz, F; Ungerechts, G; Wybranietz, W; Spiegel, M; Bernlohr, C; Cecconi, F; Gregor, M; Neubert, W; Schulze Osthoff, K; Lauer, U
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/53616
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