Relationships among dolichyl phosphate, glycoprotein synthesis, and cell culture growth.
Following treatment of Chinese hamster ovary cells with inhibitors of mevalonate biosynthesis in the presence of exogenous cholesterol, the cellular concentration of phosphorylated dolichol and the incorporation of [3H]mannose into dolichol-linked saccharides and N-linked glycoproteins declined coincident with a decline in DNA synthesis. Addition of mevalonate to the culture medium increased rates of mannose incorporation into lipid-linked saccharides and restored mannose incorporation into N-linked glycoproteins to control levels within 4 h. After an additional 4 h, synchronized DNA synthesis began. Inhibition of the synthesis of lipid-linked oligosaccharides and N-linked glycoproteins by tunicamycin prevented the induction of DNA synthesis by mevalonate, indicating that glycoprotein synthesis was required for cell division. The results suggest that the rate of cell culture growth may be influenced by the level of dolichyl phosphate acting to limit the synthesis of N-linked glycoproteins.
Jackson Laboratory, Bar Harbor, Maine 04609.
B D
BD
Kabakoff
J W
JW
Doyle
A A
AA
Kandutsch
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004287:Dolichol Monophosphate Mannose / Q000378:metabolism; D004288:Dolichol Phosphates / Q000378:metabolism*; D006023:Glycoproteins / Q000096:biosynthesis*; D007700:Kinetics; D008148:Lovastatin / Q000494:pharmacology; D008297:Male; D008358:Mannose / Q000378:metabolism; D008798:Mevalonic Acid / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008862:Microsomes, Liver / Q000378:metabolism; D011106:Polyisoprenyl Phosphates / Q000378:metabolism*; D011865:Radioisotope Dilution Technique; D014316:Tritium
D004288:Dolichol Phosphates; D006023:Glycoproteins; D011106:Polyisoprenyl Phosphates; D014316:Tritium; D004287:Dolichol Monophosphate Mannose; D002784:Cholesterol; D008148:Lovastatin; D008358:Mannose; D008798:Mevalonic Acid