title: Cyclosporin A inhibits an initial step in folding of transferrin within the endoplasmic reticulum.
abstract: As resolved by electrophoresis in non-reducing SDS gels, transferrin newly made in Hep G2 cells migrates as a very diffuse set of species. During a subsequent 1-h chase all transferrin polypeptides are converted to a single, rapidly migrating species. These changes in gel mobility are due to alterations in the pattern of disulfide bonding, are not caused by carbohydrate processing, and occur while the protein is in the rough endoplasmic reticulum. Cyclosporin A causes an approximately 10-min lag in transferrin folding, after which folding resumes at the normal rate. Cyclosporin A also retards transferrin maturation from the endoplasmic reticulum and its secretion, at concentrations that do not affect secretion of other hepatoma proteins. Neither FK506 nor rapamycin affect transferrin folding. We conclude that an initial stage in transferrin folding is accelerated by an endoplasmic reticulum peptidyl-proline isomerase that is inhibited by cyclosporin A.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142.
authors.forename: H F
authors.initials: HF
authors.lastname: Lodish
authors.forename: N
authors.initials: N
authors.lastname: Kong
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular; D003524:Cyclosporins / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008113:Liver Neoplasms; D051379:Mice; D011090:Polyenes / Q000494:pharmacology; D011233:Precipitin Tests; D011487:Protein Conformation / Q000187:drug effects*; D020123:Sirolimus; D016559:Tacrolimus; D014168:Transferrin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000900:Anti-Bacterial Agents; D003524:Cyclosporins; D011090:Polyenes; D014168:Transferrin; D020123:Sirolimus; D016559:Tacrolimus