A chemical genomics approach toward understanding the global functions of the target of rapamycin protein (TOR)
A chemical genomics approach toward understanding the global functions of the target of rapamycin protein (TOR)
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DOI：
10.1073/pnas.240444197
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发表时间：
2000-11-21
影响因子：
11.1
通讯作者：
Zheng, XFS
中科院分区：
文献类型：
--
作者：
Chan, TF;Carvalho, J;Zheng, XFS
雷帕霉素蛋白（TOR）的靶标是一种高度保守的共济失调性毛细血管扩张相关蛋白激酶，对于细胞生长至关重要。新的证据表明 TOR 信号传导非常复杂，并参与多种细胞过程。为了了解其一般功能，我们采用化学基因组学方法在基因组规模上探索 TOR 与其他酵母基因之间的遗传相互作用。在这项研究中，系统地测量了酵母基因组删除计划产生的个体删除突变体的雷帕霉素敏感性。我们的结果提供了 TOR 雷帕霉素敏感功能的全局视图。与传统的遗传分析相比，这种方法在基因组规模上提供了对遗传相互作用的简单而彻底的分析，并测量了不同可能水平的遗传相互作用。它可用于研究其他药物靶标的功能，并识别保守核心生物过程的新蛋白质成分，例如受细胞渗透性化合物干扰的 DNA 损伤检查点/修复。
The target of rapamycin protein (TOR) is a highly conserved ataxia telangiectasia-related protein kinase essential for cell growth. Emerging evidence indicates that TOR signaling is highly complex and is involved in a variety of cellular processes. To understand its general functions, we took a chemical genomics approach to explore the genetic interaction between TOR and other yeast genes on a genomic scale. In this study, the rapamycin sensitivity of individual deletion mutants generated by the Saccharomyces Genome Deletion Project was systematically measured. Our results provide a global view of the rapamycin-sensitive functions of TOR. In contrast to conventional genetic analysis, this approach offers a simple and thorough analysis of genetic interaction on a genomic scale and measures genetic interaction at different possible levels. It can be used to study the functions of other drug targets and to identify novel protein components of a conserved core biological process such as DNA damage checkpoint/repair that is interfered with by a cell-permeable chemical compound.