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Delom F, Emadali A, Cocolakis E, Lebrun JJ, Nantel A, Chevet E.
Calnexin-dependent regulation of tunicamycin-induced
apoptosis in breast carcinoma MCF-7 cells.
Cell Death Differ. 2006 Jul 21
Department of Surgery, McGill University, Montreal, Quebec,
Canada.
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 (DeltaE) partially restores their sensitivity
to tunicamycin-induced apoptosis. Indeed, we show that DeltaE
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.
PMID: 16858427
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