Functional characterization of the Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor
Functional characterization of the Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor
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DOI：
10.1007/s00294-005-0003-8
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发表时间：
2005-08-01
期刊：
影响因子：
2.5
通讯作者：
de Larrinoa, IF
中科院分区：
文献类型：
--
作者：
Santos, M;de Larrinoa, IF
钙调神经磷酸酶是一种磷蛋白磷酸酶，致力于真核生物中 Ca2+ 信号的转导。在人类病原体白色念珠菌中，钙调磷酸酶功能是细胞形态发生、唑类耐受、膜应激反应、血清中的存活和小鼠毒力所必需的。参与所有这些过程的分子机制以及下游白色念珠菌钙调神经磷酸酶的靶点仍然未知。在这里，我们使用酿酒酵母 crz1 Delta 缺陷菌株作为异源宿主，报告了白色念珠菌 Crz1 钙调磷酸酶调节转录因子的表征。 CaCrz1p 履行其酿酒酵母同源蛋白的功能，控制作用于启动子中 CDRE 序列的多个 Ca2+/钙调神经磷酸酶响应基因的表达。在模型酵母中，CaCrz1p 活性和定位受钙调神经磷酸酶调节。 CRZ1 基因的缺失使白色念珠菌对碱性阳离子和膜应激条件（包括 SDS 和抗真菌唑类药物引起的应激条件）过敏。我们的研究结果表明 CaCrz1p 是维持膜完整性所需的钙调节途径的成员。
Calcineurin is a phosphoprotein phosphatase devoted to the transduction of Ca2+-signals in eukaryotes. In the human pathogen Candida albicans, calcineurin function is required for cell morphogenesis, azole tolerance, membrane stress responses, survival in serum and virulence in mice. Molecular mechanisms as well as targets downstream C. albicans calcineurin involved in all these processes are still uncharacterized. Here we report the characterization of a C. albicans Crz1 calcineurin-regulated transcription factor using a Saccharomyces cerevisiae crz1 Delta defective strain as heterologous host. CaCrz1p fulfils the function of its S. cerevisiae homolog protein to control the expression of several Ca2+/calcineurin-responsive genes acting on the CDRE sequence in promoters. In the model yeast, CaCrz1p activity and localization are regulated by calcineurin. Deletion of CRZ1 gene renders C. albicans hypersensitive to alkaline cations and membrane stress conditions, including that elicited by SDS and antifungal azoles. Our findings indicate that CaCrz1p is member of a calcium-regulated pathway required for the maintenance of membrane integrity.