Expression of a defective mouse mammary tumor virus envelope glycoprotein precursor which binds stably to GRP78 within the lumen of the endoplasmic reticulum is associated with decreased glucocorticoid-induced apoptosis in mouse lymphoma cells (original) (raw)

Cell Death & Differentiation volume 4, pages 283–288 (1997)Cite this article

Abstract

Viral proteins inhibit apoptosis in host cells by a variety of mechanisms. This report proposes an additional mechanism, based on the interaction of a mutant mouse mammary tumor virus (MMTV) envelope glycoprotein precursor, Pr74, with the stress protein GRP78 (BiP) within the lumen of the endoplasmic reticulum (ER) (J. Biol. Chem. 268 7482 – 7488, 1993). We show that WEHI7.2 (W7.2) mouse lymphoma cells, which do not express Pr74, are more sensitive to cell death induction by the glucocorticoid hormone dexamethasone (dex), than W7MG1 cells, which were derived by infecting W7.2 cells with MMTV and therefore express Pr74 under control of the glucocorticoid-inducible MMTV promoter. Moreover, W7-ENV/N cells, derived by stably transfecting W7.2 cells with a constitutively expressed cDNA encoding mutant Pr74, were less sensitive to dex-induced cell death than control transfectant W7-ENV/− cells. Among multiple W7-ENV/N subclones, susceptibility to dex-induced cell death was inversely related to the level of Pr74 synthesis. The interaction of Pr74 with GRP78 induces an increase in GRP78 synthesis. Thus, the repression of cell death associated with Pr74 expression may be secondary to elevated synthesis of GRP78, a stress protein previously implicated in protection against cell death.

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  1. Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
    Minh Lam & Clark W Distelhorst
  2. Departments of Pathology and Biochemistry, University of Southern California Health Sciences Center, Los Angeles, 90033, California, USA
    Michael Stallcup

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  1. Minh Lam
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  2. Michael Stallcup
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  3. Clark W Distelhorst
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Correspondence toClark W Distelhorst.

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Edited by B.A. Osborne

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Lam, M., Stallcup, M. & Distelhorst, C. Expression of a defective mouse mammary tumor virus envelope glycoprotein precursor which binds stably to GRP78 within the lumen of the endoplasmic reticulum is associated with decreased glucocorticoid-induced apoptosis in mouse lymphoma cells.Cell Death Differ 4, 283–288 (1997). https://doi.org/10.1038/sj.cdd.4400249

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