Overlapping functions of the yeast oxysterol-binding protein homologues.
Overlapping functions of the yeast oxysterol-binding protein homologues.
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发表时间：
2001-03
期刊：
影响因子：
3.3
通讯作者：
Christopher T. Beh;L. G. Cool;John Phillips;J. Rine
中科院分区：
文献类型：
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作者：
Christopher T. Beh;L. G. Cool;John Phillips;J. Rine
酿酒酵母基因组编码哺乳动物氧甾醇结合蛋白（OSBP）的7个同源物，这是一种涉及脂质运输和固醇稳态的蛋白质。为了确定酵母OSBP基因家族（OSH1-OSH7）的功能，我们使用遗传学、基因组学和固醇脂分析相结合的方法来表征OSH缺失突变体。构建了所有127个OSH缺失等位基因的组合和排列。单个的OSH基因对酵母的生存不是必需的，但整个基因家族的消除是致命的。因此，家庭成员共享一个基本功能。此外，体内所有Osh蛋白的消耗破坏了固醇稳态。与影响麦角甾醇产生的突变体一样，OSH缺失等位基因的可存活组合表现出特定的甾醇相关缺陷。虽然单个OSH缺失突变体中没有一个生长缺陷，但基因表达谱显示每个突变体都有一个特征的分子表型。因此，每个基因执行不同的非必要功能，并贡献一个共同的基本功能。我们的研究结果表明，OSH基因发挥了许多由特定基因亚群定义的非必要作用，其中大多数基因至少共享一个可能与胆固醇脂质水平变化相关的重要作用。
The Saccharomyces cerevisiae genome encodes seven homologues of the mammalian oxysterol-binding protein (OSBP), a protein implicated in lipid trafficking and sterol homeostasis. To determine the functions of the yeast OSBP gene family (OSH1-OSH7), we used a combination of genetics, genomics, and sterol lipid analysis to characterize OSH deletion mutants. All 127 combinations and permutations of OSH deletion alleles were constructed. Individual OSH genes were not essential for yeast viability, but the elimination of the entire gene family was lethal. Thus, the family members shared an essential function. In addition, the in vivo depletion of all Osh proteins disrupted sterol homeostasis. Like mutants that affect ergosterol production, the viable combinations of OSH deletion alleles exhibited specific sterol-related defects. Although none of the single OSH deletion mutants was defective for growth, gene expression profiles revealed that each mutant had a characteristic molecular phenotype. Therefore, each gene performed distinct nonessential functions and contributed to a common essential function. Our findings indicated that OSH genes performed a multitude of nonessential roles defined by specific subsets of the genes and that most shared at least one essential role potentially linked to changes in sterol lipid levels.