PMID:18701708

Citation	Guérin, R, Arseneault, G, Dumont, S and Rokeach, LA (2008) Calnexin is involved in apoptosis induced by endoplasmic reticulum stress in the fission yeast. Mol. Biol. Cell 19:4404-20
Abstract	Stress conditions affecting the functions of the endoplasmic reticulum (ER) cause the accumulation of unfolded proteins. ER stress is counteracted by the unfolded-protein response (UPR). However, under prolonged stress the UPR initiates a proapoptotic response. Mounting evidence indicate that the ER chaperone calnexin is involved in apoptosis caused by ER stress. Here, we report that overexpression of calnexin in Schizosaccharomyces pombe induces cell death with apoptosis markers. Cell death was partially dependent on the Ire1p ER-stress transducer. Apoptotic death caused by calnexin overexpression required its transmembrane domain (TM), and involved sequences on either side of the ER membrane. Apoptotic death caused by tunicamycin was dramatically reduced in a strain expressing endogenous levels of calnexin lacking its TM and cytosolic tail. This demonstrates the involvement of calnexin in apoptosis triggered by ER stress. A genetic screen identified the S. pombe homologue of the human antiapoptotic protein HMGB1 as a suppressor of apoptotic death due to calnexin overexpression. Remarkably, overexpression of human calnexin in S. pombe also provoked apoptotic death. Our results argue for the conservation of the role of calnexin in apoptosis triggered by ER stress, and validate S. pombe as a model to elucidate the mechanisms of calnexin-mediated cell death.
Links	PubMed PMC2555920 Online version:10.1091/mbc.E08-02-0188
Keywords	Apoptosis; Calnexin/physiology; Cell Death; Cell Survival; Cytosol/metabolism; Endoplasmic Reticulum/metabolism; Gene Expression Regulation, Fungal; HMGB1 Protein/metabolism; Humans; Models, Biological; Mutation; Plasmids; Protein Denaturation; Schizosaccharomyces/metabolism; Schizosaccharomyces pombe Proteins/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
SCHPO:CALX	involved_in	GO:0006915: apoptotic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
SCHPO:CALX		GO:0006915: apoptosis	ECO:0000315:		P			complete

References

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