rdf:type |
|
lifeskim:mentions |
|
pubmed:issue |
1
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pubmed:dateCreated |
2005-1-24
|
pubmed:abstractText |
We describe a multicopy gene suppression screen of drug sensitivity in Saccharomyces cerevisiae that facilitates the identification of cellular targets of small molecules. An array of yeast transformants harboring a multicopy yeast genomic library was screened for resistance to growth inhibitors. Comparison of array growth patterns for several such inhibitors allowed the differentiation of general and molecule-specific genetic suppressors. Specific resistance to phenylaminopyrimidine (1), an inhibitor identified from a kinase-directed library, was associated with the overexpression of Pkc1 and a subset of downstream kinases. Components of two other pathways (pheromone response/filamentous growth and Pho85 kinase) that genetically interact with the PKC1 MAPK signaling cascade were also identified. Consistent with the suppression screen, inhibitor 1 bound to Pkc1 in yeast cell lysate and inhibited its activity in vitro. These results demonstrate the utility of this approach for the rapid deconvolution of small-molecule targets.
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
|
pubmed:status |
MEDLINE
|
pubmed:month |
Jan
|
pubmed:issn |
1074-5521
|
pubmed:author |
|
pubmed:issnType |
Print
|
pubmed:volume |
12
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
55-63
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:15664515-Drug Evaluation, Preclinical,
pubmed-meshheading:15664515-Drug Resistance, Fungal,
pubmed-meshheading:15664515-Gene Expression Regulation, Fungal,
pubmed-meshheading:15664515-Genomic Library,
pubmed-meshheading:15664515-MAP Kinase Signaling System,
pubmed-meshheading:15664515-Microbial Sensitivity Tests,
pubmed-meshheading:15664515-Molecular Structure,
pubmed-meshheading:15664515-Molecular Weight,
pubmed-meshheading:15664515-Protein Kinase C,
pubmed-meshheading:15664515-Pyridines,
pubmed-meshheading:15664515-Pyrimidines,
pubmed-meshheading:15664515-Saccharomyces cerevisiae,
pubmed-meshheading:15664515-Saccharomyces cerevisiae Proteins,
pubmed-meshheading:15664515-Sorbitol,
pubmed-meshheading:15664515-Time Factors
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pubmed:year |
2005
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pubmed:articleTitle |
A genome-wide overexpression screen in yeast for small-molecule target identification.
|
pubmed:affiliation |
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|