RAM2:: an essential gene in the prenylation pathway of Candida albicans
RAM2:: an essential gene in the prenylation pathway of Candida albicans
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DOI：
10.1099/mic.0.25887-0
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发表时间：
2003-01-01
期刊：
影响因子：
2.8
通讯作者：
White, TC
中科院分区：
文献类型：
--
作者：
Song, JL;White, TC
异戊烯化是一种翻译后蛋白质修饰过程，其导致蛋白质正确定位于细胞膜。它由真核细胞中至少三种异戊烯基转移酶（PTF）介导。RAM 2基因编码两种PTF（法尼基转移酶（FTase）和香叶基香叶基转移酶I（GGT酶1））的共同α亚基。在这项研究中，异戊二烯化途径的RAM 2基因的机会致病菌白色念珠菌进行了分析。杂合子三体试验证明RAM 2对C.白色念珠菌RAM 2 mRNA在酵母菌和菌丝生长状态下均未被北方印迹分析检测到，但被RT-PCR检测到。抑制哺乳动物PTF的药物不会改变念珠菌细胞生长，但在无细胞酶测定中它们确实抑制FTase和GGT酶I活性。遗传研究和无细胞酶测定的数据表明，药物可能无法进入念珠菌细胞质。PTF亚基的调节也在其中RAM 2在可调节启动子控制下的菌株中进行了检查。总之，本研究表明RAM 2是C.表明蛋白质异戊二烯化是该酵母中不可缺少的细胞过程。
Prenylation is a post-translational protein modification process that results in correct protein localization to membranes in the cell. It is mediated by at least three prenyltransferases (PTFs) in eukaryotic cells. The RAM2 gene encodes the common alpha-subunit of two PTFs, farnesyltransferase (FTase) and geranylgeranyltransferase I (GGTase 1). In this study, the RAM2 gene of the prenylation pathway in the opportunistic pathogen Candida albicans was analysed. The heterozygote trisomy test was used to demonstrate that RAM2 is essential to the viability of C. albicans. RAM2 mRNA in the yeast and hyphae growth states was not detected by Northern blot analysis, but was detected by RT-PCR. Drugs that inhibit mammalian PTFs do not alter Candida cell growth, but they do inhibit FTase and GGTase I activities in cell-free enzyme assays. The data from genetic studies and cell-free enzyme assays suggest that the drugs may not have access to the Candida cytoplasm. The regulation of PTF subunits was also examined in a strain in which RAM2 was under the control of a regulable promoter. Overall, this study demonstrated that RAM2 is essential to C. albicans, indicating that protein prenylation is an indispensable cellular process in this yeast.