title: Suppression of stress protein GRP78 induction in tumor B/C10ME eliminates resistance to cell mediated cytotoxicity.
abstract: Tumor cells undergo self-destruction when incubated with cytotoxic T-cells (CTL) consistent with the observation that suppression of target protein synthesis causes resistance to apoptosis. Resistance to CTL is also induced by stress, suggesting that pathways exist suppressing apoptosis. Here we examine whether stress induced lysis resistance to CTL and tumor necrosis factor alpha involves stress proteins GRP78 and GRP94. We show that inhibition of GRP78 synthesis by transfection of cells with grp78 antisense vector pRSV-78WO leads to inability to induce resistance to CTL or tumor necrosis factor alpha. Resistance induced in untransfected cells is reversible upon stress removal and correlates with GRP78 rephosphorylation, consistent with the notion that phosphorylated GRP78 is nonfunctional. The possibility that GRP78 plays a role in defense against CTL mediated apoptosis is supported by the finding that CTL but not CD4+ cells express a high level of unphosphorylated GRP78.
authors.affiliation: Department of Microbiology, University of Southern California, Los Angeles 90033-0800.
authors.forename: S
authors.initials: S
authors.lastname: Sugawara
authors.forename: K
authors.initials: K
authors.lastname: Takeda
authors.forename: A
authors.initials: A
authors.lastname: Lee
authors.forename: G
authors.initials: G
authors.lastname: Dennert
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis*; D003602:Cytotoxicity, Immunologic; D000091342:Endoplasmic Reticulum Chaperone BiP; D005354:Fibrosarcoma / Q000276:immunology / Q000473:pathology; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018832:Molecular Chaperones; D010766:Phosphorylation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D018832:Molecular Chaperones; D014409:Tumor Necrosis Factor-alpha