CONTROL OF RAB5 AND RAB7 EXPRESSION BY THE ISOPRENOID PATHWAY

Rab proteins are small molecular mass GTP-ases involved in the regulat ion of vescicular transport. The ability of rab proteins to carry out their role in intracellular membrane traffic requires the post-transla tional attachment to their C-terminus of a geranylgeranyl group, an is oprenoid lipid moiety derived from mevalonate. Here we report that dep letion of intracellular mevalonate by lovastatin in FRTL-5 thyroid cel ls specifically resulted in a four-fold increase of Rab5 and Rab7 prot ein levels. This increase was reversed within 4 h upon addition of mev alonate. Similarly lovastatin also induced, at same extent, mRNA level s. Lovastatin effect was not common to other prenylated proteins. More over incubation with cycloheximide abolished the observed increase in lovastatin treated cells, suggesting that the effect is mediated by ne wly synthesized protein. These findings demonstrate that Rab5 and Rab7 expression are regulated by the isoprenoid pathway. (C) 1998 Academic Press.