학술논문
Systematic Interactome Mapping and Genetic Perturbation Analysis of a C. elegans TGF-β Signaling Network
Document Type
Article
Author
Tewari, Muneesh; Hu, Patrick J.; Ahn, Jin Sook; Ayivi-Guedehoussou, Nono; Vidalain, Pierre-Olivier; Li, Siming; Milstein, Stuart; Armstrong, Chris M.; Boxem, Mike; Butler, Maurice D.; Busiguina, Svetlana; Rual, Jean-François; Ibarrola, Nieves; Chaklos, Sabrina T.; Bertin, Nicolas; Vaglio, Philippe; Edgley, Mark L.; King, Kevin V.; Albert, Patrice S.; Vandenhaute, Jean
Source
Subject
*GENETICS
*GENE mapping
*MYC proteins
*MAMMALS
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Language
ISSN
1097-2765
Abstract
To initiate a system-level analysis of C. elegans DAF-7/TGF-β signaling, we combined interactome mapping with single and double genetic perturbations. Yeast two-hybrid (Y2H) screens starting with known DAF-7/TGF-β 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-β pathway mutant animals, identified nine DAF-7/TGF-β 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-β signaling. Our results reveal substantial molecular complexity in DAF-7/TGF-β signal transduction. Integrating interactome maps with systematic genetic perturbations may be useful for developing a systems biology approach to this and other signaling modules. [Copyright &y& Elsevier]