Oligosaccharide trimming plays a role in the endoplasmic reticulum-associated degradation of tyrosinase.
The effect of glucosidase and mannosidase inhibitors on the ER-associated degradation of tyrosinase was assessed in transiently transfected COS-7 cells. We found that the glucosidase inhibitors castanospermine and deoxynojirimycin had very little effect on tyrosinase degradation, whereas the mannosidase inhibitors deoxymannojirimycin and kifunensine significantly delayed the rate of tyrosinase degradation as measured by pulse-chase analysis. In addition, we show that tyrosinase degradation is sensitive to the proteasome inhibitor lactacystin and that tyrosinase associates with endogenous calnexin in COS-7 cells. Our data support a model of tyrosinase degradation that involves mannose trimming, calnexin association, and the retrograde transport of tyrosinase from the ER to the cytosol for proteasomal degradation. The pathways of tyrosinase degradation have important ramifications with regard to the exact types of antigenic epitopes that are presented to the immune system.
Wang
Y
Y
Immunology Program, H. Lee Moffitt Cancer Center and Research Institute, and Department of Biochemistry and Molecular Biology, University of South Florida College of Medicine, Tampa, Florida, 33612, USA.
Androlewicz
M J
MJ
D017485:1-Deoxynojirimycin / Q000494:pharmacology; D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000941:Antigens / Q000378:metabolism; D019556:COS Cells; D002135:Calcium-Binding Proteins / Q000378:metabolism; D037281:Calnexin; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005959:Glucosidases / Q000037:antagonists & inhibitors; D006801:Humans; D007212:Indolizines / Q000494:pharmacology; D008361:Mannosidases / Q000037:antagonists & inhibitors; D008954:Models, Biological; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D011233:Precipitin Tests; D013997:Time Factors; D054836:Indolizidines
D017485:1-Deoxynojirimycin; D000111:Acetylcysteine; D000470:Alkaloids; D000941:Antigens; D002135:Calcium-Binding Proteins; D037281:Calnexin; D015853:Cysteine Proteinase Inhibitors; D004791:Enzyme Inhibitors; D005959:Glucosidases; D007212:Indolizines; D008361:Mannosidases; D014442:Monophenol Monooxygenase; C065629:kifunensine; C067713:lactacystin; C037806:castanospermine; D054836:Indolizidines