Leukaemia inhibitory factor or oncostatin M induction of Swiss 3T3 cells does not require mevalonic acid synthesis nor protein isoprenylation to initiate DNA replication.
Leukaemia inhibitory factor (LIF) or Oncostatin M (OSM), both mitogens for Swiss mouse 3T3 cells, triggers initiation of DNA synthesis without the requirement for mevalonic acid. Thus, Lovastatin (LOV), an inhibitor of the hydroxy methylglutaryl CoA (HMGCoA) reductase, does not block LIF or OSM induced DNA replication and cell multiplication. In contrast, increasing concentrations of LOV from 1 to 60 microM block the mitogenic action of PGF(2alpha) by decreasing the number of cells capable of entering S-phase and dividing. This inhibition by LOV can be reversed by addition of mevanolactone (MEV), an analogue of mevalonic acid. Thus, LIF or OSM triggers initiation of DNA replication independently of mevalonic acid synthesis and therefore without the involvement of isoprenylation of various signalling proteins.
Sauane
Moira
M
Instituto de Investigaciones Bioquímicas Fundación Instituto Leloir, Av. Patricias Argentinas 435, (1405), Buenos Aires, Argentina.
Coso
Omar A
OA
Giulianelli
Sebastián
S
Giráldez
Adrian N
AN
Rudland
Philip S
PS
Jimenez de Asua
Luis
L
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects*; D015237:Dinoprost / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008148:Lovastatin / Q000494:pharmacology; D008798:Mevalonic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D018832:Molecular Chaperones / Q000494:pharmacology*; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D017368:Protein Prenylation; D011506:Proteins; D041701:Swiss 3T3 Cells
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008934:Mitogens; D018832:Molecular Chaperones; C508352:Osm protein, mouse; D010455:Peptides; D011506:Proteins; D053683:Oncostatin M; C015367:mevalonolactone; D008148:Lovastatin; D015237:Dinoprost; D008798:Mevalonic Acid