Glucocorticoid-regulated compartmentalization of cell surface-associated glycoproteins in rat hepatoma cells: evidence for an independent response that requires receptor function and de novo RNA synthesis.
The role of glucocorticoid hormones in the compartmentalization of cell surface-associated mouse mammary tumor virus (MMTV) glycoproteins was examined in M1.54, a cloned line of MMTV-infected rat hepatoma tissue culture cells. The expression of cellular [2-3H]mannose-labeled and cell surface 125I-labeled MMTV glycoproteins was examined throughout a time course of exposure to dexamethasone, a synthetic glucocorticoid. Posttranslational localization of cell surface MMTV glycoproteins required 6 h of exposure to hormone and occurred approximately 4 h after their initial production in an intracellular fraction. This regulated localization to the cell surface correlated with glucocorticoid receptor occupancy and was inhibited by exposure to RU 38486, a powerful antagonist of glucocorticoid-mediated responses. Cell surface immunoprecipitation demonstrated that actinomycin D, an inhibitor of de novo RNA synthesis, prevented regulated expression of cell surface viral glycoproteins, suggesting that newly synthesized cellular components mediate this process. The localization of cell surface MMTV glycoproteins appeared normal in a transcriptional variant (CR1) that produces basal levels of MMTV RNA and glycoprotein precursors in the presence of dexamethasone. Thus, regulated compartmentalization of viral glycoproteins is not an obligate consequence of a critical precursor concentration. Taken together, our results suggest that posttranslational trafficking of cell surface-destined MMTV glycoproteins resulted from an independent glucocorticoid hormone response that required receptor function and de novo RNA synthesis.
D000818:Animals; D000956:Antigens, Viral / Q000235:genetics*; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D005796:Genes / Q000187:drug effects; D005814:Genes, Viral / Q000187:drug effects; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D007700:Kinetics; D008114:Liver Neoplasms, Experimental / Q000235:genetics*; D008324:Mammary Tumor Virus, Mouse / Q000187:drug effects / Q000235:genetics*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats; D012191:Retroviridae Proteins / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic
D000956:Antigens, Viral; D006023:Glycoproteins; D012191:Retroviridae Proteins; D003907:Dexamethasone