Transcription factors CgUPC2A and CgUPC2B regulate ergosterol biosynthetic genes in Candida glabrata
Transcription factors CgUPC2A and CgUPC2B regulate ergosterol biosynthetic genes in Candida glabrata
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DOI：
10.1111/j.1365-2443.2010.01470.x
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发表时间：
2011-01-01
期刊：
影响因子：
2.1
通讯作者：
Miyazaki, Yoshitsugu
中科院分区：
文献类型：
--
作者：
Nagi, Minoru;Nakayama, Hironobu;Miyazaki, Yoshitsugu
Zn[2]-Cys[6]双核转录因子Upc 2 p和Ecm 22 p调控酿酒酵母麦角甾醇生物合成和外源甾醇摄取相关基因的表达。我们在病原真菌光滑念珠菌中鉴定了两个UPC 2/ECM 22同源物，我们将其命名为CgUPC 2A和CgUPC 2B。研究了这两个基因对固醇稳态的贡献。缺乏CgUPC 2A（upc 2A Delta）的细胞表现出对甾醇生物合成抑制剂氟康唑和洛伐他汀的敏感性增强，而upc 2B Delta突变细胞与野生型细胞一样对药物敏感。在厌氧条件下，upc 2A Delta细胞的生长也严重减弱。洛伐他汀处理增强了麦角固醇生物合成基因，ERG 2和ERG 3在野生型和upc 2B δ细胞，但不是在upc 2A δ细胞的表达。同样，血清诱导的ERG 2和ERG 3的表达在upc 2A Delta细胞中完全受损，但在upc 2B Delta细胞中不受影响，而血清诱导的固醇转运蛋白基因CgAUS 1的表达在upc 2A Delta和upc 2B Delta细胞中均受损。这些结果表明，在C. glabrata CgUPC 2A而不是CgUPC 2B是负责维持固醇稳态以及对固醇抑制剂敏感性的基因的主要转录调节因子。
Zn[2]-Cys[6] binuclear transcription factors Upc2p and Ecm22p regulate the expression of genes involved in ergosterol biosynthesis and exogenous sterol uptake in Saccharomyces cerevisiae. We identified two UPC2/ECM22 homologues in the pathogenic fungus Candida glabrata which we designated CgUPC2A and CgUPC2B. The contribution of these two genes to sterol homeostasis was investigated. Cells that lack CgUPC2A (upc2A Delta) exhibited enhanced susceptibility to the sterol biosynthesis inhibitors, fluconazole and lovastatin, whereas upc2B Delta-mutant cells were as susceptible to the drugs as wild-type cells. The growth of upc2A Delta cells was also severely attenuated under anaerobic conditions. Lovastatin treatment enhanced the expression of ergosterol biosynthetic genes, ERG2 and ERG3 in wild-type and upc2B Delta but not in upc2A Delta cells. Similarly, serum-induced expression of ERG2 and ERG3 was completely impaired in upc2A Delta cells but was unaffected in upc2B Delta cells, whereas serum-induced expression of the sterol transporter gene CgAUS1 was impaired in both upc2A Delta and upc2B Delta cells. These results suggest that in C. glabrata CgUPC2A but not in CgUPC2B is the main transcriptional regulator of the genes responsible for maintaining sterol homeostasis as well as susceptibility to sterol inhibitors.