Function of mevalonate in tobacco cell proliferation

We have used mevinolin, an inhibitor of 3-hydroxy-3-methylglutaryl-CoA redu ctase, to study the importance of mevalonic acid (UVA) for cell cycle progr ession of tobacco (Nicotiana tabacum L.) BY-2 (TBY-2) cells. Previously we have shown that in principal mevinolin blocks cells mainly at the end of G1 phase, but that cells are sensitive towards the inhibitor at the end of mi tosis/entry G1 phase (Hemmerlin & Each, 1998). The mevinolin-induced cell-c ycle arrest was reversed by addition of exogenous MVA. It is shown that blo ckage of MVA synthesis might lead to variations in intracellular pH, which could be involved in the regulation of cell proliferation. SDS-PAGE analyse s of total proteins and GTP-blot analyses indicate mevinolin-induced change s in the pattern, which can be reversed by addition of MVA. In preliminary experiments it has been demonstrated that artificial increase of the cytoso lic pH partially released mevinolin-treated cells from the arrest in late G 1 phase. A model is presented of how such proteins and pH variations could interact with cell cycle regulation.