Rce1酶切Bex2调控胶质瘤生长的研究

Rce1是谷氨酸膜内蛋白酶家族的第一个已知成员。其与人类癌症密切相关，是因其参与了CAAX蛋白的酶切。Ras是研究较为深入的CAAX蛋白，异戊烯化的Ras可被Rce1酶切并被ICMT甲基化后定位到细胞膜上，发挥促进肿瘤生长的作用。我们研究证实Bex2可促进胶质瘤的生长。同时Bex2羧基端也含有一CAAX序列。基于我们发现缺失CAAX序列的Bex2促进细胞增殖的能力明显下降，本项目拟以脑胶质瘤标本，培养的细胞及裸鼠为研究对象，以Rce1为研究切入点，从分子、细胞与整体水平研究：Rce1在胶质瘤中的表达及对细胞增殖/凋亡、侵袭/迁移的影响；Rce1对Bex2的酶切作用及对胶质瘤细胞生长的影响。阐明Rce1及其酶切Bex2对胶质瘤细胞生长的作用机制。预期研究结果将揭示：Rce1是调控胶质瘤生长的关键分子，Bex2被Rce1酶切后发挥作用，为胶质瘤的分子靶向治疗提供新的理论依据及治疗靶点。

Rce1 is the founding member of glutamate IMPs. It is closely related to cancer development, as Rce1 is responsible for endoproteolytic processing of the vast majority of CAAX proteins. RAS family, which almost all contain the CAAX motif, are particularly interesting because of their promoting role in oncogenesis. Following prenylation, ras usually undergo endoproteolytic processing by Rce1 and then methylation by isoprenylcysteine carboxyl methyltransferase (ICMT) trafficking to cellular membranes. Our preliminary data showed that Bex2 can promote the glioma cell growth. Meanwhile Bex2 also contains a CAAX carboxy-terminal sequence, deleting the sequence the promoting role of Bex2 on cell proliferation decreased significantly. Thus, by using the glioma specimens, cultured glioma cells and nude mice, we determine to study Rce1 expression level in glioma, the role of Rce1 in glioma cell proliferation / apoptosis and invasion / migration. The proteolysis role of Rce1 on Bex2 in gliomagenesis. Our results will not only clear the role of Rce1 in gliomagenesis, but also elucidate the proteolysis role of Rce1 on Bex2 in gliomagenesis, provide potential targets for molecular targeting therapy of brain gliomas.