Laezza C, Bucci C, Santillo M, Bruni C B, Bifulco M
Centro di Endocrinologia ed Oncologia Sperimentale G. Salvatore del CNR, Italy.
Biochem Biophys Res Commun. 1998 Jul 30;248(3):469-72. doi: 10.1006/bbrc.1998.9007.
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.
Rab蛋白是参与囊泡运输调节的小分子量GTP酶。Rab蛋白在细胞内膜运输中发挥作用的能力需要在其C末端翻译后附着一个香叶基香叶基基团，这是一种源自甲羟戊酸的类异戊二烯脂质部分。在这里，我们报告说，洛伐他汀在FRTL-5甲状腺细胞中耗尽细胞内甲羟戊酸会导致Rab5和Rab7蛋白水平特异性增加四倍。添加甲羟戊酸后4小时内这种增加就会逆转。同样，洛伐他汀也在相同程度上诱导mRNA水平。洛伐他汀的作用并非其他异戊二烯化蛋白所共有。此外，用环己酰亚胺孵育消除了洛伐他汀处理细胞中观察到的增加，这表明该作用是由新合成的蛋白质介导的。这些发现表明，Rab5和Rab7的表达受类异戊二烯途径的调节。
