Control of Rab5 and Rab7 expression by the isoprenoid pathway.
Rab proteins are small molecular mass GTP-ases involved in the regulation of vescicular transport. The ability of rab proteins to carry out their role in intracellular membrane traffic requires the post-translational attachment to their C-terminus of a geranylgeranyl group, an isoprenoid lipid moiety derived from mevalonate. Here we report that depletion of intracellular mevalonate by lovastatin in FRTL-5 thyroid cells specifically resulted in a four-fold increase of Rab5 and Rab7 protein levels. This increase was reversed within 4 h upon addition of mevalonate. Similarly lovastatin also induced, at same extent, mRNA levels. Lovastatin effect was not common to other prenylated proteins. Moreover incubation with cycloheximide abolished the observed increase in lovastatin treated cells, suggesting that the effect is mediated by newly synthesized protein. These findings demonstrate that Rab5 and Rab7 expression are regulated by the isoprenoid pathway.
Centro di Endocrinologia ed Oncologia Sperimentale G. Salvatore del CNR, Italy.
C
C
Laezza
C
C
Bucci
M
M
Santillo
C B
CB
Bruni
M
M
Bifulco
D000818:Animals; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000187:drug effects; D007700:Kinetics; D008148:Lovastatin / Q000494:pharmacology*; D008798:Mevalonic Acid / Q000378:metabolism; D017368:Protein Prenylation; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D013961:Thyroid Gland; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins; D000090802:rab7 GTP-Binding Proteins
D012333:RNA, Messenger; D000090802:rab7 GTP-Binding Proteins; C000716466:rab7 GTP-binding proteins, rat; D003513:Cycloheximide; D008148:Lovastatin; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins; D008798:Mevalonic Acid