Abstract
A genetically defined pathway orchestrates the removal of 131 of the 1090 somatic cells generated during the development of the hermaphrodite nematode Caenorhabditis elegans. Regulation of apoptosis is highly evolutionarily conserved and the nematode cell death pathway is a valuable model for studying mammalian apoptotic pathways, the dysregulation of which can contribute to numerous diseases. The nematode caspase CED-3 is ultimately responsible for the destruction of worm cells in response to apoptotic signals, but it must first be activated by CED-4. CED-9 inhibits programmed cell death and considerable data have demonstrated that CED-9 can directly bind and inhibit CED-4. However, it has been suggested that CED-9 may also directly inhibit CED-3. In this study, we used a yeast-based system and biochemical approaches to explore this second potential mechanism of action. While we confirmed the ability of CED-9 to inhibit CED-4, our data argue that CED-9 can not directly inhibit CED-3.
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Abbreviations
- AFC:
-
7-amino-4-(trifluoromethyl)coumarin
- Apaf-1:
-
apoptotic protease activating factor-1
- Bcl-2:
-
B-cell lymphoma-2
- GFP:
-
green fluorescent protein
- GST:
-
glutathione-S-transferase
- PCR:
-
polymerase chain reaction
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Acknowledgements
We thank Trevor Lithgow and Lena Burri for their generous donation of the anti-GFP antibody and the p416-MET25-GFPS65 T plasmid. We thank David Vaux for providing helpful suggestions about the manuscript and for stimulating discussions. This study was supported by the Australian Research Council and the National Health and Medical Research Council of Australia.
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Jabbour, A., Ho, Pk., Puryer, M. et al. The Caenorhabditis elegans CED-9 protein does not directly inhibit the caspase CED-3, in vitro nor in yeast. Cell Death Differ 11, 1309–1316 (2004). https://doi.org/10.1038/sj.cdd.4401501
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DOI: https://doi.org/10.1038/sj.cdd.4401501
