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Regulation of calnexin sub-cellular localization modulates endoplasmic reticulum stress-induced apoptosis in MCF-7 cells

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Abstract

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.

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Abbreviations

ER:

endoplasmic reticulum

siRNA:

small interfering RNA

SDS-PAGE:

sodium dodecyl sulfate polyacrylamide gel electrophoresis

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Author notes

  1. Frédéric Delom & Delphine Fessart

    Present address: Institute of Cell and Molecular Science, Barts and The London, Queen Mary’s School of Medicine and Dentistry, 4 Newark Street, London, E1 2AT, United Kingdom

Authors and Affiliations

  1. Department of Surgery, McGill University, 687 Pine Avenue West, Montreal, QC, H3A 1A1, Canada

    Frédéric Delom & Eric Chevet

  2. Department of Medicine, McGill University, Montreal, Quebec, Canada

    Delphine Fessart & Eric Chevet

  3. Department of Anatomy & Cell Biology, McGill University, Montreal, Quebec, Canada

    Eric Chevet

  4. INSERM, E362, Université Victor Segalen Bordeaux 2, Bordeaux, 33076, France

    Eric Chevet

Authors
  1. Frédéric Delom
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  2. Delphine Fessart
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  3. Eric Chevet
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Correspondence to Eric Chevet.

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Delom, F., Fessart, D. & Chevet, E. Regulation of calnexin sub-cellular localization modulates endoplasmic reticulum stress-induced apoptosis in MCF-7 cells. Apoptosis 12, 293–305 (2007). https://doi.org/10.1007/s10495-006-0625-4

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  • DOI: https://doi.org/10.1007/s10495-006-0625-4

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