Differential interaction of branch-specific inhibitors of isoprenoid biosynthesis with cell cycle progression in tobacco BY-2 cells

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR), which cat alyzes the formation of mevalonic acid (MVA), can be specifically blocked b y mevinolin, Inhibition of HMGR in vivo leads to an arrest in cell cycle pr ogression in tobacco (Nicotiana tabacum L. Bright Yellow 2) cells. As MVA i n plants is the common precursor of a myriad of isoprenoid products synthes ized in the cytosol and mitochondria, it is difficult to identify among suc h MVA-dependent molecules those whose lack may lead to cell cycle arrest. I n an attempt to do so, branch-specific inhibitors of the cytosolic isopreno id pathway downstream from MVA were used to study their capacity to block c ell cycle progression, The effects of squalestatin (sterol biosynthesis inh ibitor), chaetomellic acid A and patulin (protein prenyltransferase (PT) in hibitors) and tunicamycin (inhibitor of dolichol-dependent protein glycosyl transferase, thus mimicking the effect of an absence of dolichol) were com pared to those induced by mevinolin, In this way, squalestatin and chaetome llic acid were identified as behaving like true cell cycle inhibitors, in t hat they led to a specific arrest in the cell cycle, However, they did not exactly mimic the mevinolin-induced effects. Patulin proved to be of high g eneral toxicity, which suggests that it may affect other reactions besides blockage of protein isoprenylation, Finally, tunicamycin efficiently blocke d growth of cell suspension cultures, but did not arrest the cells in a spe cific phase of the cell cycle. Results are discussed in the context of a be tter understanding of the essential implication of isoprenoids in plant cel l cycle progression.