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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2004-3-2
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pubmed:abstractText |
To initiate a system-level analysis of C. elegans DAF-7/TGF-beta signaling, we combined interactome mapping with single and double genetic perturbations. Yeast two-hybrid (Y2H) screens starting with known DAF-7/TGF-beta pathway components defined a network of 71 interactions among 59 proteins. Coaffinity purification (co-AP) assays in mammalian cells confirmed the overall quality of this network. Systematic perturbations of the network using RNAi, both in wild-type and daf-7/TGF-beta pathway mutant animals, identified nine DAF-7/TGF-beta signaling modifiers, seven of which are conserved in humans. We show that one of these has functional homology to human SNO/SKI oncoproteins and that mutations at the corresponding genetic locus daf-5 confer defects in DAF-7/TGF-beta signaling. Our results reveal substantial molecular complexity in DAF-7/TGF-beta signal transduction. Integrating interactome maps with systematic genetic perturbations may be useful for developing a systems biology approach to this and other signaling modules.
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pubmed:grant |
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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 |
Feb
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pubmed:issn |
1097-2765
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pubmed:author |
pubmed-author:AhnJin SookJS,
pubmed-author:AlbertPatrice SPS,
pubmed-author:ArmstrongChris MCM,
pubmed-author:Ayivi-GuedehoussouNonoN,
pubmed-author:BertinNicolasN,
pubmed-author:BoxemMikeM,
pubmed-author:BusiguinaSvetlanaS,
pubmed-author:ButlerMaurice DMD,
pubmed-author:ChaklosSabrina TST,
pubmed-author:EdgleyMark LML,
pubmed-author:HuPatrick JPJ,
pubmed-author:IbarrolaNievesN,
pubmed-author:KingKevin VKV,
pubmed-author:LiSimingS,
pubmed-author:MilsteinStuartS,
pubmed-author:PandeyAkhileshA,
pubmed-author:RiddleDonald LDL,
pubmed-author:RualJean-FrançoisJF,
pubmed-author:RuvkunGaryG,
pubmed-author:TewariMuneeshM,
pubmed-author:VaglioPhilippeP,
pubmed-author:VandenhauteJeanJ,
pubmed-author:VidalMarcM,
pubmed-author:VidalainPierre-OlivierPO
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pubmed:issnType |
Print
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pubmed:day |
27
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pubmed:volume |
13
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
469-82
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:14992718-Animals,
pubmed-meshheading:14992718-Caenorhabditis elegans,
pubmed-meshheading:14992718-Caenorhabditis elegans Proteins,
pubmed-meshheading:14992718-Cell Line,
pubmed-meshheading:14992718-Chromosome Mapping,
pubmed-meshheading:14992718-Cosmids,
pubmed-meshheading:14992718-Gene Expression Regulation, Developmental,
pubmed-meshheading:14992718-Genes, Helminth,
pubmed-meshheading:14992718-Genomics,
pubmed-meshheading:14992718-Humans,
pubmed-meshheading:14992718-Kidney,
pubmed-meshheading:14992718-Models, Biological,
pubmed-meshheading:14992718-Mutation,
pubmed-meshheading:14992718-Open Reading Frames,
pubmed-meshheading:14992718-Proteome,
pubmed-meshheading:14992718-RNA, Small Interfering,
pubmed-meshheading:14992718-Signal Transduction,
pubmed-meshheading:14992718-Transfection,
pubmed-meshheading:14992718-Transforming Growth Factor beta,
pubmed-meshheading:14992718-Transgenes,
pubmed-meshheading:14992718-Two-Hybrid System Techniques
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pubmed:year |
2004
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pubmed:articleTitle |
Systematic interactome mapping and genetic perturbation analysis of a C. elegans TGF-beta signaling network.
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pubmed:affiliation |
Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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