Role of N-linked glycosylation in cell-cycle progression and initiation of DNA synthesis in tumor-transformed human fibroblasts.
In this study we show that proliferation of cycling tumor-transformed human fibroblasts (line 90VAV1) is blocked specifically in G1 by HMG CoA reductase inhibition. This inhibition also resulted in a drastic depression of N-linked glycosylation, measured as incorporation of radioactive glucosamine into acid-insoluble material. Following addition of mevalonate to cells arrested by HMG CoA reductase inhibitors, the depression of N-linked glycosylation was overcome and the cells initiated DNA synthesis. However, if the mevalonate-induced increase in protein glycosylation was prevented, due to addition of tunicamycin (an inhibitor of N-linked glycosylation), the cells were not able to proliferate. If instead tunicamycin was added 4 h after the addition of mevalonate, the cells synthesized DNA normally. Upon addition of tunicamycin, to cycling cells the progression through G1 was blocked in a similar way to that following HMG CoA reductase inhibition. Taken together, our data provide strong evidence for involvement of N-linked glycosylation in the mevalonate-controlled cell cycle progression and growth activation of tumor-transformed human fibroblasts.
Carlberg
M
M
Department of Tumor Pathology, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden.
Larsson
O
O
D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology*; D006031:Glycosylation; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000378:metabolism; D013268:Stimulation, Chemical; D014415:Tunicamycin / Q000502:physiology
D004273:DNA, Neoplasm; D006888:Hydroxycholesterols; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009363:Neoplasm Proteins; D014415:Tunicamycin; C007997:25-hydroxycholesterol; D008148:Lovastatin