Study on Activated Prenylated Derivertives-Containing Liposomes Controllable for Switching of Cell Cycle

本研究的主要目的是阐明与细胞内转导相关的蛋白质异戊二烯化的生物学意义和异戊二烯化的机制，为了分析异戊二烯类化合物作为胆固醇合成途径的中间代谢产物的作用，我们开发了一种新的方法，将这些中间代谢产物--异戊二烯化的脂质体掺入通过抑制HMG-CoA还原酶而静止的细胞中，作为胆固醇合成途径中的限速酶。该方法观察到类异戊二烯化合物香叶基香叶基焦磷酸（GGPP）对甲状腺细胞DNA合成有影响，并调节细胞周期。我们还利用大肠杆菌进行脂质代谢酶基因的功能检测，克隆了GGPP合酶的cDNA。

The major purpose of the present study is to clarify the biological significance of prenylation of proteins associated with intracellular transduction and the mechanism on prenylation.To analysis on the roles of isopenoide compounds, as an intermediated metabollite of the cholesterol synthesis pathway, we developed a novel method to incorporate those intermediates-encapslated liposomes into cells rested by inhibiting HMG-CoA reductase, as a rate-limiting enzyme in the cholesterol synthesis pathway. This method provided the observation that geranylgeranyl pyrophosphate (GGPP), one of isoprenoid compounds, has a role on hormone-dependent DNA synthesis in thyroid cells and results in regulating those cell cycle. It was also observed that GGPP is a critical compound for cortical nuerons to protect cell death.We also cloned cDNA of GGPP synthase by detecting a function assay of genes for lipid metabolism enzymes, using E.coli.