Deficiency in caspase-9 or caspase-3 induces compensatory caspase activation

Zheng, Timothy S.; Hunot, Stéphane; Kuida, Keisuke; Momoi, Takashi; Srinivasan, Anu; Nicholson, Donald W.; Lazebnik, Yuri; Flavell, Richard A.

doi:10.1038/81343

Cited by 287 publications

(214 citation statements)

References 31 publications

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“…Recent cloning of DFF45/ICAD homologues raise the possibility that other DFF45/ DFF40 complexes exist which can be activated independently of caspase-3. Indeed, in support of this idea it has been demonstrated that, in the absence of caspase-3, hepatocyte cells induce compensatory caspase activation, such as caspase-6 (Zheng et al, 2000). This could also be the case for MCF-7 cells, as we have shown that…”

Section: Effect Of Staurosporine On Bcl-2 Bcl-x L Bak and Bax Proteisupporting

confidence: 74%

Apoptotic mechanisms in T47D and MCF-7 human breast cancer cells

et al. 2002

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To investigate the mechanisms underlying apoptosis in breast cancer cells, staurosporine was used as an apoptotic stimulus in the human breast cancer cell lines MCF-7 and T47D. Staurosporine induced dose and time dependent increases in DNA fragmentation which was abrogated by z-VAD-fmk. MCF-7 cells did not express caspase-3, suggesting that DNA fragmentation occurred in the absence of caspase-3 and that other caspases may be involved. Staurosporine induced DEVDase activity in T47D cells suggesting the involvement of caspase-3 and/or caspase-7, yet there was no DEVDase activity in MCF-7 cells, probably ruling out the involvement caspase-7. However, staurosporine induced the cleavage of pro-caspase-6 in MCF-7 cells, but not in T47D cells. Caspase dependent PARP cleavage was detected in MCF-7 cells at 3 h, whereas only partial PARP cleavage was detected in T47D cells and then only after 24 h. Moreover, staurosporine led to cytochrome c release at 2 h in MCF-7 cells and 6 h in T47D cells. In addition, a time dependent and caspase-independent reduction of the mitochondrial transmembrane potential was observed; which appeared to occur after the release of cytochrome c. Translocation of Bax from the cytosol to mitochondria was observed in both cell types, and this preceded cytochrome c release in both T47D and MCF-7 cells. Apoptotic events in both cell types differ temporally, involving activation of different caspases and mitochondrial changes.

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Section: Effect Of Staurosporine On Bcl-2 Bcl-x L Bak and Bax Proteisupporting

confidence: 74%

Apoptotic mechanisms in T47D and MCF-7 human breast cancer cells

et al. 2002

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“…Similarly, analysis of genetic knockouts in mouse has revealed that Caspase-3 is essential in some cell types for apoptosis, but not in others, and that additional effector caspases can compensate for the loss of Caspase-3. 36 Interestingly, labeling of drICE 17 mutant embryos with cleaved caspase-3 (Caspase-3*) antibody produced a wildtype pattern. This is puzzling because the Caspase-3* pattern does not match the AO-and TUNEL patterns of drICE 17 mutants (Figure 3).…”

Section: Partial Redundancy Between Drice and Dcp-1mentioning

confidence: 99%

The effector caspases drICE and dcp-1 have partially overlapping functions in the apoptotic pathway in Drosophila

et al. 2006

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Caspases are essential components of the apoptotic machinery in both vertebrates and invertebrates. Here, we report the isolation of a mutant allele of the Drosophila effector caspase drICE as a strong suppressor of hid-(head involution defective-) induced apoptosis. This mutant was used to determine the apoptotic role of drICE. Our data are consistent with an important function of drICE for developmental and irradiation-induced cell death. Epistatic analysis suggests that drICE acts genetically downstream of Drosophila inhibitor of apoptosis protein 1 (Diap1). However, although cell death is significantly reduced in drICE mutants in all assays, it is not completely blocked. A double-mutant analysis between drICE and death caspase-1 (dcp-1), another effector caspase, reveals that some cells (type I) strictly require drICE for apoptosis, whereas other cells (type II) require either drICE or dcp-1. Thus, these data demonstrate a barely appreciated complexity in the apoptotic pathway, and are consistent with current models about effector caspase regulation in both vertebrates and invertebrates.

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“…The timing of death varies among regions of the brain, from the early embryonic to the early postnatal periods. Mice lacking many of the other caspases, such as caspase 1, 2, 6, 11, or 12, do not have an obvious neuronal phenotype (Kuida et al, 1995;Bergeron et al, 1998;Namura et al, 1998;Wang et al, 1998;Zheng et al, 2000), but these caspases may play a role in regional pruning of neurons or in the plasticity of the nervous system.…”

Section: Developmental Death Pathways Inmentioning

confidence: 99%

“…This seems to be a significant problem with apoptotic genes, where phenotypic selection in developing embryos can severely alter normal expression patterns, as has been shown in caspase 2, 3, and 9 null mice (Zheng et al, 2000;Troy et al, 2001). Thus, removal of nerve growth factor (NGF) from cultured postnatal sympathetic neurons may induce parallel caspase pathways, and the dominant pathway depends on the relative concentrations of anti-and proapoptotic proteins (Troy et al, 2001).…”

Section: Developmental Death Pathways Inmentioning

confidence: 99%

Caspases on the brain

Troy

Salvesen

2002

J of Neuroscience Research

105

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The basic mechanisms that underlie neurodegenerative diseases are unknown. Loss of function of specific regions of the brain is due to incapacitation of cells that constitute those regions. Cells can simply stop functioning normally (neurons may cease to transmit signals), or they may die. There is now evidence that the pathology of several neurodegenerative diseases is due to inappropriate apoptosis. This being the case, an understanding of the mediators of apoptosis, their identities, and their role in orchestrating death would be a vital step toward remedying the diseases. The central components of apoptotic pathways, proteases of the caspase family, are present in latent forms in all nucleated cells. Their activity is balanced by specific activation and inactivation events, and the molecular and biochemical controls have been well established in vitro and in model transformed cell lines. In this Mini‐Review, we consider the current status of the basic control mechanisms and how these may be subverted during neurodegeneration. © 2002 Wiley‐Liss, Inc.

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Deficiency in caspase-9 or caspase-3 induces compensatory caspase activation

Cited by 287 publications

References 31 publications

Apoptotic mechanisms in T47D and MCF-7 human breast cancer cells

Apoptotic mechanisms in T47D and MCF-7 human breast cancer cells

The effector caspases drICE and dcp-1 have partially overlapping functions in the apoptotic pathway in Drosophila

Caspases on the brain

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