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Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13227-32.

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

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  • 1Departments of Pathology and Immunology and Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.

Abstract

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.

PMID:
11078525
[PubMed - indexed for MEDLINE]
PMCID:
PMC27207
Free PMC Article

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