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Mol. Cells 2002; 13(2): 194-201

Published online January 1, 1970

© The Korean Society for Molecular and Cellular Biology

Signaling and Function of Caspase and c-Jun N-terminal Kinase in Cisplatin-induced Apoptosis

Myoung-Sook Koo, Young-Guen Kwon, Joon-Hong Park, Won-Jin Choi, TimothyR. Billiar, Young-Myeong Kim

Abstract

Caspases and c-Jun N-terminal kinase (JNK) are acti-vated in tumor cells during induction of apoptosis. We investigated the signaling cascade and function of these enzymes in cisplatin-induced apoptosis. Treat-ment of Jurkat T-cells with cisplatin induced cell death with DNA fragmentation and activation of cas-pase and JNK. Bcl-2 overexpression suppressed activa-tion of both enzymes, whereas p35 and CrmA inhib-ited only the DEVDase (caspase-3-like) activity, indi-cating that the activation of these enzymes may be dif-ferentially regulated. Cisplatin induced apoptosis with the cytochrome c release and caspase-3 activation in both wild-type and caspase-8-deficient JB-6 cells, while the Fas antibody induced these apoptotic events only in wild-type cells. This indicates that caspase-8 activation is required for Fas-mediated apoptosis, but not cisplatin-induced cell death. On the other hand, cisplatin induced the JNK activation in both the wild-type and JB-6 cells, and the caspase-3 inhibitor Z-DEVD-fmk did not inhibit this activation. The JNK overexpression resulted in a higher JNK activity, AP-1 DNA binding activity, and metallothionein expression than the empty vector-transfected cells following cis-platin treatment. It also partially protected the cells from cisplatin-induced apoptosis by decreasing DEVDase activity. These data suggest that the cis-platin-induced apoptotic signal is initiated by the cas-pase-8-independent cytochrome c release, and the JNK activation protects cells from cisplatin-induced apop-tosis via the metallothionein expression.

Keywords JNK., Apoptosis, Cytochrome c, Caspase, Cisplatin

Article

Research Article

Mol. Cells 2002; 13(2): 194-201

Published online April 30, 2002

Copyright © The Korean Society for Molecular and Cellular Biology.

Signaling and Function of Caspase and c-Jun N-terminal Kinase in Cisplatin-induced Apoptosis

Myoung-Sook Koo, Young-Guen Kwon, Joon-Hong Park, Won-Jin Choi, TimothyR. Billiar, Young-Myeong Kim

Abstract

Caspases and c-Jun N-terminal kinase (JNK) are acti-vated in tumor cells during induction of apoptosis. We investigated the signaling cascade and function of these enzymes in cisplatin-induced apoptosis. Treat-ment of Jurkat T-cells with cisplatin induced cell death with DNA fragmentation and activation of cas-pase and JNK. Bcl-2 overexpression suppressed activa-tion of both enzymes, whereas p35 and CrmA inhib-ited only the DEVDase (caspase-3-like) activity, indi-cating that the activation of these enzymes may be dif-ferentially regulated. Cisplatin induced apoptosis with the cytochrome c release and caspase-3 activation in both wild-type and caspase-8-deficient JB-6 cells, while the Fas antibody induced these apoptotic events only in wild-type cells. This indicates that caspase-8 activation is required for Fas-mediated apoptosis, but not cisplatin-induced cell death. On the other hand, cisplatin induced the JNK activation in both the wild-type and JB-6 cells, and the caspase-3 inhibitor Z-DEVD-fmk did not inhibit this activation. The JNK overexpression resulted in a higher JNK activity, AP-1 DNA binding activity, and metallothionein expression than the empty vector-transfected cells following cis-platin treatment. It also partially protected the cells from cisplatin-induced apoptosis by decreasing DEVDase activity. These data suggest that the cis-platin-induced apoptotic signal is initiated by the cas-pase-8-independent cytochrome c release, and the JNK activation protects cells from cisplatin-induced apop-tosis via the metallothionein expression.

Keywords: JNK., Apoptosis, Cytochrome c, Caspase, Cisplatin

Mol. Cells
Jun 30, 2023 Vol.46 No.6, pp. 329~398
COVER PICTURE
The cellular proteostasis network is adaptively modulated upon cellular stress, thereby protecting cells from proteostasis collapse. Heat shock induces the translocation of misfolded proteins and the chaperone protein HSP70 into nucleolus, where nuclear protein quality control primarily occurs. Nuclear RNA export factor 1 (green), nucleolar protein fibrillarin (red), and nuclei (blue) were visualized in NIH3T3 cells under basal (left) and heat shock (right) conditions (Park et al., pp. 374-386).

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