A chemical genomics approach toward understanding the global functions of the target of rapamycin protein (TOR).

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.
Mesh Terms:
1-Phosphatidylinositol 3-Kinase, Cell Cycle Proteins, Fungal Proteins, Gene Expression Regulation, Fungal, Genomics, Humans, Microbial Sensitivity Tests, Microtubules, Phosphotransferases (Alcohol Group Acceptor), Protein Kinases, Ribosomal Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Sirolimus, Transcription, Genetic, Ubiquitins, Vacuoles
Proc. Natl. Acad. Sci. U.S.A.
Date: Nov. 21, 2000
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