The role of N-linked glycosylation in the regulation of activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and proliferation of SV40-transformed 3T3 cells.
The effects of glycosylation inhibitors on the proliferation of SV40-transformed 3T3 cells (SV-3T3) were examined in vitro. Whereas swainsonine and castanospermine, which inhibit distal steps in the glycosylational processing, exerted marginal or no effects on cell proliferation, a proximal inhibitor, tunicamycin, efficiently decreased the rate of DNA synthesis and also inhibited the activity of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase. The inhibitory effects of tunicamycin on cell proliferation could be partially reversed by addition of dolichol, a metabolite in the pathway regulated by HMG-CoA reductase. This finding suggests that tunicamycin exerts at least one of its effects on cell proliferation by modulating the activity of HMG-CoA reductase.
Larsson
O
O
Department of Tumour Pathology, Karolinska Hospital, Stockholm, Sweden.
Engström
W
W
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D006031:Glycosylation; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D051379:Mice; D013539:Simian virus 40; D014415:Tunicamycin / Q000494:pharmacology*
D014415:Tunicamycin; D006903:Hydroxymethylglutaryl CoA Reductases