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.
Chan
T F
TF
Departments of Pathology and Immunology and Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Carvalho
J
J
Riles
L
L
Zheng
X F
XF
D018797:Cell Cycle Proteins; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D023281:Genomics; D006801:Humans; D008826:Microbial Sensitivity Tests; D008870:Microtubules / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases; D014158:Transcription, Genetic; D014452:Ubiquitins / Q000502:physiology; D014617:Vacuoles / Q000502:physiology
D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011494:Protein Kinases; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D014452:Ubiquitins; C546842:MTOR protein, human; C083324:TOR1 protein, S cerevisiae; C081135:TOR2 protein, S cerevisiae