1. ¹Department of Surgery, McGill University, Montreal, Quebec, Canada
2. ²Montreal Proteomics Network, McGill University, Montreal, Quebec, Canada
3. ³Department of Medicine, McGill University, Montreal, Quebec, Canada
4. ⁴Biotechnology Research Institute, National Research Council of Canada, Montreal, Quebec, Canada
5. ⁵Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada

Correspondence: E Chevet, McGill University, Department of Surgery, Royal Victoria Hospital, Room H6-34, 687 Pine Avenue West, Montreal, QC, Canada H3A 1A1. Tel: +1 514 934 1934 ext 35468; Fax: +1 514 843 1411; E-mail: eric.chevet@mcgill.ca

Received 7 December 2005; Revised 9 May 2006; Accepted 14 June 2006; Published online 21 July 2006.

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 (E) partially restores their sensitivity to tunicamycin-induced apoptosis. Indeed, we show that E 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.