Preferential synthesis of the 78-Kd glucose-regulated protein in glucocorticoid-treated S49 mouse lymphoma cells.
To investigate the mechanism of glucocorticoid-induced lymphocytolysis, we used two-dimensional gel electrophoresis to analyze the effect of dexamethasone on the synthesis of individual proteins in S49 mouse lymphoma cells. We found that synthesis of a 78-Kd protein is preferentially maintained following dexamethasone treatment, at a time when the synthesis of most other cellular proteins is decreased. Synthesis of this protein could also be induced by tunicamycin, suggesting that it might be the 78-Kd glucose-regulated protein (GRP78). The identity of the 78-Kd protein with GRP78 was confirmed by limited chymotryptic mapping and immunoprecipitation analysis. Preferential synthesis of GRP78 in dexamethasone-treated cells was not secondary to alterations in the glycosylation of cellular proteins. Significantly, steady-state levels of GRP78 mRNA were unchanged following dexamethasone treatment. Preferential synthesis of GRP78 in glucocorticoid-treated S49 cells may reflect the unique property of GRP78 mRNA to be translated under conditions that interfere with the translation of most other cellular mRNAs. GRP78 is a highly conserved protein that is essential for cell viability. Preferential synthesis of GRP78 may be a protective response to metabolic events that interfere with normal mRNA translation in glucocorticoid-treated mouse lymphoma cells.
Lam
M
M
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH.
Vimmerstedt
L J
LJ
Schlatter
L K
LK
Hensold
J O
JO
Distelhorst
C W
CW
D000818:Animals; D001345:Autoradiography; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002918:Chymotrypsin; D003907:Dexamethasone / Q000494:pharmacology*; D015180:Electrophoresis, Gel, Two-Dimensional; D000091342:Endoplasmic Reticulum Chaperone BiP; D006031:Glycosylation; D006360:Heat-Shock Proteins; D007143:Immunoglobulin Heavy Chains; D008223:Lymphoma / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018832:Molecular Chaperones; D010449:Peptide Mapping; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014415:Tunicamycin / Q000494:pharmacology
D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D007143:Immunoglobulin Heavy Chains; D018832:Molecular Chaperones; D012333:RNA, Messenger; D014415:Tunicamycin; D003907:Dexamethasone; D002918:Chymotrypsin