Analysis of Role of the Yeast UBP6-encoded Hydrolase

酵母 UBP6 编码的水解酶的作用分析

• 批准号: 6504774
• 负责人: JOHN E GOLIN
• 金额: $ 13.36万
• 依托单位: CATHOLIC UNIVERSITY OF AMERICA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-04 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6504774
• 关键词: Saccharomyces; enzyme activity; fungal genetics; gene expression; gene mutation; genetic translation; hydrolase; membrane transport proteins; microarray technology; multidrug resistance; northern blottings; nucleic acid hybridization; polymerase chain reaction; transcription factor; ubiquitin

DESCRIPTION (provided by applicant): In yeast, broad-spectrum resistance inhibitors is mediated by a series of membrane transporters that are members of the ABC superfamily and use ATP to power drug efflux. The genes involved include PDR5, YOR1, and SNQ2. These loci are in turn regulated by zinc cluster transcriptionfactors encoded by the PDR1, YRR1 (PDR2) and PDR3 genes. Dominant gain-of-function mutations in PDR2 cause hyper-resistance via the over expression of YOR1, SNQ2 and at least one other target. Curiously, this target requires the presence of the Ubp6 ubiquitin hydrolase. Null mutations in UBP6 create hypersensitivity to inhibitors of protein translation. Using microarray analysis, the Ubp6-dependent PDR2 target will be identified. Subsequent genetic analysis will identify other genes that work along with UBP6. This work, along with some simple molecular cytology should help determine the precise role of this hydrolase in the cell.

描述（由申请人提供）：在酵母中，广谱抗性 抑制剂是由一系列膜转运蛋白介导的，这些转运蛋白是 ABC 超家族并使用 ATP 为药物流出提供动力。涉及的基因 包括 PDR5、YOR1 和 SNQ2。这些位点依次受锌簇调控 由 PDR1、YRR1 (PDR2) 和 PDR3 基因编码的转录因子。 PDR2 的显性功能获得性突变通过过度抵抗导致高耐药性。 YOR1、SNQ2 和至少一个其他靶标的表达。奇怪的是，这个目标 需要 Ubp6 泛素水解酶的存在。 UBP6 无效突变 对蛋白质翻译抑制剂产生超敏反应。使用微阵列 分析后，将确定 Ubp6 依赖性 PDR2 靶标。后续遗传 分析将识别与 UBP6 一起发挥作用的其他基因。这项工作，沿着 通过一些简单的分子细胞学检查应该有助于确定 细胞内有这种水解酶。