Glucocorticoid-dependent maturation of mouse mammary tumor virus glycoproteins in mouse lymphoma cells: isolation of variants with constitutive viral protein maturation and normal glucocorticoid receptor function.
The posttranslational maturation and cell surface localization of mouse mammary tumor virus (MMTV) envelope glycoproteins is regulated by glucocorticoid hormone in mouse T-lymphoma cell line W7MG1. Only when the cells are cultured with glucocorticoid is the MMTV envelope precursor, Pr74, converted efficiently to the two mature proteolytic products, gp52 and gp33. By immunological selection we have isolated protein-processing variants that express the mature viral proteins constitutively on the cell surface. The rate of synthesis of Pr74 is indistinguishable in variant and wild-type cells, but the variants efficiently convert Pr74 to gp52 and gp33 even when grown without the hormone. The variant phenotype persists when the variant cells are fused with uninfected wild-type cells to form somatic cell hybrids, indicating that the variant phenotype resulted from expression of a new or altered function that is not expressed in wild-type cells grown without glucocorticoid. Although the specific gene whose structure or regulation is altered in the variant has not yet been determined, some possibilities have been eliminated. First, the number and function of the glucocorticoid receptors in the variant cells was normal, suggesting that alterations in this protein were not responsible for the variant phenotype. Second, comparison by two-dimensional gel electrophoresis of gp52 produced in variant and wild-type cells revealed no differences in size or charge, indicating no gross differences in the processing of the viral proteins in the variant and wild-type cells.
Byravan
S
S
Department of Pathology, University of Southern California School of Medicine, Los Angeles 90033.
Stallcup
M R
MR
D000818:Animals; D000957:Antigens, Viral, Tumor / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D014644:Genetic Variation / Q000235:genetics; D005938:Glucocorticoids / Q000494:pharmacology*; D006023:Glycoproteins / Q000032:analysis / Q000502:physiology*; D006822:Hybrid Cells / Q000378:metabolism; D008223:Lymphoma / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D010641:Phenotype; D011965:Receptors, Glucocorticoid / Q000378:metabolism / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
D000957:Antigens, Viral, Tumor; D005938:Glucocorticoids; D006023:Glycoproteins; D011965:Receptors, Glucocorticoid; D014764:Viral Proteins; C040612:glycoprotein 52 antigen, Mouse mammary tumor virus