A stress-inducible rat liver endoplasmic reticulum protein, ERp29

Authors

  • Souren Mkrtchian,

    1. Department of Medical Biochemistry and Biophysics and Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institute, Stockholm
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  • Che Fang,

    1. Department of Medical Biochemistry and Biophysics and Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institute, Stockholm
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  • Ulf Hellman,

    1. Institute for Cancer Research, Biomedical Center, Uppsala, Sweden
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  • Magnus Ingelman-Sundberg

    1. Department of Medical Biochemistry and Biophysics and Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institute, Stockholm
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  • Correspondence to S. Mkrtchian, Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institute, PO Box 201, S-171 77 Stockholm, Sweden

  • Fax: +46 8 317875.

  • E-mail:soumkr@ki.se

  • URL:http://www.imm.ki.se/moltox

  • Abbreviations. ER, endoplasmic reticulum; GRP78/BiP, glucose-regulated protein 78/immunoglobulin-heavy-chain-binding protein; GRP94, glucose-regulated protein 94; Hsp70, heat-shock protein 70; Hsp90, heat-shock protein 90; PDI, protein disulfide isomerase.

  • Note. The nucleotide sequence data reported here have been submitted to the GenBank sequence databank and are available under accession number U36482.

Abstract

We have isolated, cDNA cloned and characterised a 29-kDa protein (ERp29), containing a C-terminal endoplasmic reticulum(ER)-retrieval signal, from the rat liver ER. ERp29 was induced to high levels in the rat hepatoma cells under metabolic stress conditions known to cause an aberrant accumulation of proteins in the ER [(e.g. culture in presence of the Ca2+ ionophore A23187, inhibitors of Ca2+-ATPase (thapsigargin), intracellular protein transport (brefeldin A), or protein N-glycosylation (tunicamycin)]. Experimental evidence of its localisation in the luminal compartment of the ER was obtained by topology studies including immunofluorescence microscopy, in vitro translation and proteinase protection assay. ERp29 constitutes about 0.1 % of the rat hepatic microsomal proteins and is constitutively expressed in all rat tissues examined, as evident from northern blot analysis. In rat hepatoma cells ERp29 was found to be associated with the abundant molecular chaperone/stress protein BiP/GRP78 and this interaction was significantly enhanced after treatment with tunicamycin and A23187. Taken together, these results suggest that ERp29 is a member of the stress-response machinery of the ER.

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