Microarray-based method for monitoring yeast overexpression strains reveals small-molecule targets in TOR pathway.
Identifieur interne : 001770 ( Main/Exploration ); précédent : 001769; suivant : 001771Microarray-based method for monitoring yeast overexpression strains reveals small-molecule targets in TOR pathway.
Auteurs : Rebecca A. Butcher [États-Unis] ; Bhupinder S. Bhullar ; Ethan O. Perlstein ; Gerald Marsischky ; Joshua Labaer ; Stuart L. SchreiberSource :
- Nature chemical biology [ 1552-4450 ] ; 2006.
Descripteurs français
- KwdFr :
- Aminoquinoléines (pharmacologie), Analyse par réseau de protéines (MeSH), Antifongiques (pharmacologie), Conception de médicament (MeSH), Phosphatidylinositol 3-kinases (génétique), Phosphatidylinositol 3-kinases (métabolisme), Phosphotransferases (Alcohol Group Acceptor) (génétique), Phosphotransferases (Alcohol Group Acceptor) (métabolisme), Plasmides (génétique), Protéines de Saccharomyces cerevisiae (génétique), Protéines de Saccharomyces cerevisiae (métabolisme), Régulation de l'expression des gènes fongiques (effets des médicaments et des substances chimiques), Saccharomyces cerevisiae (croissance et développement), Saccharomyces cerevisiae (génétique), Saccharomyces cerevisiae (métabolisme), Sirolimus (pharmacologie).
- MESH :
- croissance et développement : Saccharomyces cerevisiae.
- effets des médicaments et des substances chimiques : Régulation de l'expression des gènes fongiques.
- génétique : Phosphatidylinositol 3-kinases, Phosphotransferases (Alcohol Group Acceptor), Plasmides, Protéines de Saccharomyces cerevisiae, Saccharomyces cerevisiae.
- métabolisme : Phosphatidylinositol 3-kinases, Phosphotransferases (Alcohol Group Acceptor), Protéines de Saccharomyces cerevisiae, Saccharomyces cerevisiae.
- pharmacologie : Aminoquinoléines, Antifongiques, Sirolimus.
- Analyse par réseau de protéines, Conception de médicament.
English descriptors
- KwdEn :
- Aminoquinolines (pharmacology), Antifungal Agents (pharmacology), Drug Design (MeSH), Gene Expression Regulation, Fungal (drug effects), Phosphatidylinositol 3-Kinases (genetics), Phosphatidylinositol 3-Kinases (metabolism), Phosphotransferases (Alcohol Group Acceptor) (genetics), Phosphotransferases (Alcohol Group Acceptor) (metabolism), Plasmids (genetics), Protein Array Analysis (MeSH), Saccharomyces cerevisiae (genetics), Saccharomyces cerevisiae (growth & development), Saccharomyces cerevisiae (metabolism), Saccharomyces cerevisiae Proteins (genetics), Saccharomyces cerevisiae Proteins (metabolism), Sirolimus (pharmacology).
- MESH :
- chemical , genetics : Phosphatidylinositol 3-Kinases, Phosphotransferases (Alcohol Group Acceptor), Saccharomyces cerevisiae Proteins.
- chemical , metabolism : Phosphatidylinositol 3-Kinases, Phosphotransferases (Alcohol Group Acceptor), Saccharomyces cerevisiae Proteins.
- chemical , pharmacology : Aminoquinolines, Antifungal Agents, Sirolimus.
- drug effects : Gene Expression Regulation, Fungal.
- genetics : Plasmids, Saccharomyces cerevisiae.
- growth & development : Saccharomyces cerevisiae.
- metabolism : Saccharomyces cerevisiae.
- Drug Design, Protein Array Analysis.
Abstract
Identification of the cellular targets of small-molecule hits in phenotypic screens is a central challenge in the development of small molecules as biological tools and potential therapeutics. To facilitate the process of small-molecule target identification, we developed a global, microarray-based method for monitoring the growth of pools of yeast strains, each overexpressing a different protein, in the presence of small molecules. Specifically, the growth of Saccharomyces cerevisiae strains harboring approximately 3,900 different overexpression plasmids was monitored in the presence of rapamycin, which inhibits the target of rapamycin (TOR) proteins. TOR was successfully identified as a candidate rapamycin target, and many additional gene products were implicated in the TOR signaling pathway. We also characterized the mechanism of LY-83583, a small-molecule suppressor of rapamycin-induced growth inhibition. These data enabled functional links to be drawn between groups of genes implicated in the TOR pathway, identified several candidate targets for LY-83583, and suggested a role for mitochondrial respiration in mediating rapamycin sensitivity.
DOI: 10.1038/nchembio762
PubMed: 16415861
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
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To facilitate the process of small-molecule target identification, we developed a global, microarray-based method for monitoring the growth of pools of yeast strains, each overexpressing a different protein, in the presence of small molecules. Specifically, the growth of Saccharomyces cerevisiae strains harboring approximately 3,900 different overexpression plasmids was monitored in the presence of rapamycin, which inhibits the target of rapamycin (TOR) proteins. TOR was successfully identified as a candidate rapamycin target, and many additional gene products were implicated in the TOR signaling pathway. We also characterized the mechanism of LY-83583, a small-molecule suppressor of rapamycin-induced growth inhibition. These data enabled functional links to be drawn between groups of genes implicated in the TOR pathway, identified several candidate targets for LY-83583, and suggested a role for mitochondrial respiration in mediating rapamycin sensitivity.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">16415861</PMID><DateCompleted><Year>2006</Year><Month>03</Month><Day>14</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Print">1552-4450</ISSN><JournalIssue CitedMedium="Print"><Volume>2</Volume><Issue>2</Issue><PubDate><Year>2006</Year><Month>Feb</Month></PubDate></JournalIssue><Title>Nature chemical biology</Title><ISOAbbreviation>Nat Chem Biol</ISOAbbreviation></Journal><ArticleTitle>Microarray-based method for monitoring yeast overexpression strains reveals small-molecule targets in TOR pathway.</ArticleTitle><Pagination><MedlinePgn>103-9</MedlinePgn></Pagination><Abstract><AbstractText>Identification of the cellular targets of small-molecule hits in phenotypic screens is a central challenge in the development of small molecules as biological tools and potential therapeutics. To facilitate the process of small-molecule target identification, we developed a global, microarray-based method for monitoring the growth of pools of yeast strains, each overexpressing a different protein, in the presence of small molecules. Specifically, the growth of Saccharomyces cerevisiae strains harboring approximately 3,900 different overexpression plasmids was monitored in the presence of rapamycin, which inhibits the target of rapamycin (TOR) proteins. TOR was successfully identified as a candidate rapamycin target, and many additional gene products were implicated in the TOR signaling pathway. We also characterized the mechanism of LY-83583, a small-molecule suppressor of rapamycin-induced growth inhibition. 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ValidYN="Y"><LastName>LaBaer</LastName><ForeName>Joshua</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Schreiber</LastName><ForeName>Stuart L</ForeName><Initials>SL</Initials></Author></AuthorList><Language>eng</Language><DataBankList CompleteYN="Y"><DataBank><DataBankName>PubChem-Substance</DataBankName><AccessionNumberList><AccessionNumber>7982025</AccessionNumber><AccessionNumber>7982026</AccessionNumber></AccessionNumberList></DataBank></DataBankList><GrantList CompleteYN="Y"><Grant><GrantID>GM38627</GrantID><Acronym>GM</Acronym><Agency>NIGMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01-HG002923</GrantID><Acronym>HG</Acronym><Agency>NHGRI NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. 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(Massachusetts)</li></settlement><orgName><li>Université Harvard</li></orgName></list><tree><noCountry><name sortKey="Bhullar, Bhupinder S" sort="Bhullar, Bhupinder S" uniqKey="Bhullar B" first="Bhupinder S" last="Bhullar">Bhupinder S. Bhullar</name><name sortKey="Labaer, Joshua" sort="Labaer, Joshua" uniqKey="Labaer J" first="Joshua" last="Labaer">Joshua Labaer</name><name sortKey="Marsischky, Gerald" sort="Marsischky, Gerald" uniqKey="Marsischky G" first="Gerald" last="Marsischky">Gerald Marsischky</name><name sortKey="Perlstein, Ethan O" sort="Perlstein, Ethan O" uniqKey="Perlstein E" first="Ethan O" last="Perlstein">Ethan O. Perlstein</name><name sortKey="Schreiber, Stuart L" sort="Schreiber, Stuart L" uniqKey="Schreiber S" first="Stuart L" last="Schreiber">Stuart L. Schreiber</name></noCountry><country name="États-Unis"><region name="Massachusetts"><name sortKey="Butcher, Rebecca A" sort="Butcher, Rebecca A" uniqKey="Butcher R" first="Rebecca A" last="Butcher">Rebecca A. Butcher</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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