Regulation of calnexin sub-cellular localization modulates endoplasmic reticulum stress-induced apoptosis in MCF-7 cells.
The endoplasmic reticulum (ER) is the cellular compartment where proteins enter the secretory pathway, undergo post-translational modifications and acquire a correct conformation. If these functions are chronically altered, specific ER stress signals are triggered to promote cell death through the intrinsic apoptotic pathway. Here, we show that tunicamycin causes significant alteration of calnexin sub-cellular distribution in MCF-7 cells. Interestingly, this correlates with the absence of both tunicamycin-induced calnexin phosphorylation as well as tunicamycin-induced cell death. Under these conditions, calnexin-associated Bap31, an ER integral membrane protein, is subjected to a caspase-8 cleavage pattern within a specific sub-compartment of the ER. These results suggest that MCF-7 resistance to ER stress-induced apoptosis is partially mediated by the expression level of calnexin which in turn controls its sub-cellular localization, and its association with Bap31. These data may delineate a resistance mechanism to the ER stress-induced intrinsic apoptotic pathway.
Delom
Frédéric
F
Department of Surgery, McGill University, 687 Pine Avenue West, Montreal, QC, H3A 1A1, Canada.
Fessart
Delphine
D
Chevet
Eric
E
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D037281:Calnexin / Q000172:deficiency / Q000378:metabolism*; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000473:pathology*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013347:Subcellular Fractions / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D014415:Tunicamycin / Q000494:pharmacology
C091247:BCAP31 protein, human; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D014415:Tunicamycin; D037281:Calnexin