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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
15
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pubmed:dateCreated |
2007-4-11
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pubmed:abstractText |
Small molecule inhibitors provide powerful tools to characterize highly dynamic and complex eukaryotic cell pathways such as those mediating membrane traffic. However, a lack of easy and generalizable assays has constrained identification of novel inhibitors despite availability of diverse chemical libraries. Here, we report a facile growth-based strategy in yeast to screen for pathway-specific inhibitors. The approach uses well characterized synthetic genetic growth defects to guide design of cells genetically sensitized for inhibition of chosen pathways. With this strategy, we identified a family of piperazinyl phenylethanone compounds as inhibitors of traffic between the trans-Golgi network (TGN) and endosomes that depends on the clathrin adaptor complex AP-1. The compounds did not significantly alter other trafficking pathways involving the TGN or endosomes, indicating specificity. Compound treatment also altered localization of AP-1 in mammalian cells. These previously uncharacterized inhibitors will be useful for future studies of clathrin-mediated transport in yeast, and potentially in other organisms. Furthermore, the easily automated technology should be adaptable for identification of inhibitors of other cellular processes.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-10564262,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-10628971,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-10811610,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-11157985,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-11309404,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-11408593,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-11687498,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-11879634,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-12571274,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-14661025,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-14708007,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-15190181,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-15539461,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-16110319,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-16121259,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-16309778,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-16760313,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-16790491,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-16901791,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-2675311,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-7615679,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-8157009,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-8273152,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-8276891,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-8391002,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-8909536,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-9171338,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-9335339,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-9353181,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-9412470,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17404221-9717241
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
104
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6235-40
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:17404221-Adaptor Protein Complex 1,
pubmed-meshheading:17404221-Adaptor Proteins, Vesicular Transport,
pubmed-meshheading:17404221-Cell Survival,
pubmed-meshheading:17404221-Chitin,
pubmed-meshheading:17404221-Endosomes,
pubmed-meshheading:17404221-Genes, Lethal,
pubmed-meshheading:17404221-Molecular Structure,
pubmed-meshheading:17404221-Mutation,
pubmed-meshheading:17404221-Organic Chemicals,
pubmed-meshheading:17404221-Protein Transport,
pubmed-meshheading:17404221-Saccharomyces cerevisiae Proteins,
pubmed-meshheading:17404221-Yeasts,
pubmed-meshheading:17404221-trans-Golgi Network
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pubmed:year |
2007
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pubmed:articleTitle |
Composite synthetic lethal identification of membrane traffic inhibitors.
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pubmed:affiliation |
Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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