Analysis of Role of the Yeast UBP6-encoded Hydrolase
Analysis of Role of the Yeast UBP6-encoded Hydrolase
批准号:
6504774
负责人:
JOHN E GOLIN
金额:
$13.36万
依托单位国家:
美国
项目类别:
财政年份:
2002
资助国家:
美国
项目状态:
已结题
起止时间:
2002-09-04 至 2005-08-31
中文摘要
性状(由申请方提供):在酵母菌中,广谱耐药性
抑制剂是由一系列膜转运蛋白介导的,这些膜转运蛋白是
ABC超家族和使用ATP来驱动药物外排。涉及的基因
包括PDR 5、YOR 1和SNQ 2。这些位点又受锌簇的调控
由PDR1、YRR1(PDR2)和PDR3基因编码的转录因子。
PDR2中的显性功能获得性突变通过过度表达而引起超耐药
YOR 1、SNQ 2和至少一种其它靶标的表达。奇怪的是,这个目标
需要Ubp6泛素水解酶的存在。UBP6中的突变
产生对蛋白质翻译抑制剂的超敏反应。使用微阵列
通过分析,将鉴定Ubp6依赖性PDR2靶标。后续基因
分析将鉴定与UBP 6一起沿着工作的其它基因。这项工作,沿着
一些简单的分子细胞学应该有助于确定
这种水解酶。
英文摘要
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.
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会议论文
Molecular Genetic Analysis of Pdr5p, a Major Yeast Multidrug Transporter
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批准号:7073770
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项目类别:
-
资助金额:$19.56万
-
财政年份:2006
-
负责人:JOHN E GOLIN
-
依托单位:
SMALL INSTRUMENTATION GRANT
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批准号:3524184
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项目类别:
-
资助金额:$0.5万
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财政年份:1991
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负责人:JOHN E GOLIN
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依托单位:
ANALYZE GENE SMR3 CONFERRING MULTIPLE DRUG RESISTANCE
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批准号:3438707
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项目类别:
-
资助金额:$10.45万
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财政年份:1989
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负责人:JOHN E GOLIN
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依托单位:
海外基金