Abstract
The endoplasmic reticulum (ER) has evolved specific mechanisms to ensure protein folding as well as the maintenance of its own homeostasis. When these functions are not achieved, specific ER stress signals are triggered to activate either adaptive or apoptotic responses. Here, we demonstrate that MCF-7 cells are resistant to tunicamycin-induced apoptosis. We show that the expression level of the ER chaperone calnexin can directly influence tunicamycin sensitivity in this cell line. Interestingly, the expression of a calnexin lacking the chaperone domain (ΔE) partially restores their sensitivity to tunicamycin-induced apoptosis. Indeed, we show that ΔE acts as a scaffold molecule to allow the cleavage of Bap31 and thus generate the proapoptotic p20 fragment. Utilizing the ability of MCF-7 cells to resist tunicamycin-induced apoptosis, we have characterized a molecular mechanism by which calnexin regulates ER-stress-mediated apoptosis in a manner independent of its chaperone functions but dependent of its binding to Bap31.
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Abbreviations
- ER:
-
endoplasmic reticulum
- siRNA:
-
small interfering RNA
- SDS-PAGE:
-
sodium dodecyl sulfate polyacrylamide gel electrophoresis
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Acknowledgements
We thank the Chevet's lab and D Fessart for critical reading of the manuscript. This work was supported by a grant from the Canadian Institutes for Health Research to EC. FD was supported in part by an operating grant from Genome Quebec/Canada to the Montreal Proteomics Network – the cell map project. EC is a junior scholar from the FRSQ. AN was supported by the NRC Genome Health Initiative. This is NRC publication number 46182.
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Delom, F., Emadali, A., Cocolakis, E. et al. Calnexin-dependent regulation of tunicamycin-induced apoptosis in breast carcinoma MCF-7 cells. Cell Death Differ 14, 586–596 (2007). https://doi.org/10.1038/sj.cdd.4402012
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DOI: https://doi.org/10.1038/sj.cdd.4402012
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