@article{9f1417c56c4547fb9248d140dc9b9b51,
title = "Systematic interactome mapping and genetic perturbation analysis of a C. elegans TGF-β signaling network",
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.",
author = "Muneesh Tewari and Hu, {Patrick J.} and Ahn, {Jin Sook} and Nono Ayivi-Guedehoussou and Vidalain, {Pierre Olivier} and Siming Li and Stuart Milstein and Armstrong, {Chris M.} and Mike Boxem and Butler, {Maurice D.} and Svetlana Busiguina and Rual, {Jean Fran{\c c}ois} and Nieves Ibarrola and Chaklos, {Sabrina T.} and Nicolas Bertin and Philippe Vaglio and Edgley, {Mark L.} and King, {Kevin V.} and Albert, {Patrice S.} and Jean Vandenhaute and Akhilesh Pandey and Riddle, {Donald L.} and Gary Ruvkun and Marc Vidal",
note = "Funding Information: We thank Cathy Gunther, Peifeng Ren, Sharon Cantor, David Hill, Denis Dupuy, Marian Walhout, Simon Boulton, J{\'e}r{\^o}me Reboul, and Shivapriya Ramaswamy for helpful discussions and advice; Roger Greenberg and David Hill for critical review of the manuscript; Suzanne Clark for technical assistance; Atisha Chatterjee for expert DNA sequencing; Alan Coulson for the gift of cosmid strains; Yuji Kohara and Garth Patterson for a W01G7.1/ daf-5 cDNA; Kunxin Luo and Yin Sun for SNON cDNA; William P. Shiemann for the p3TP-lux reporter plasmid; Julie Ahringer for several RNAi feeding constructs; Andrew Fire for the GFP expression vector; and Anneliese Schaefer and Mike Nonet for primers used in the DNA dimorphism analysis. Some strains were provided by the Caenorhabditis Genetics Center (University of Minnesota, St. Paul). This work was funded by DHHS grant GM60151 (to D.L.R.), Physician Postdoctoral Fellowships from the Howard Hughes Medical Institute (to M.T. and P.J.H.), a Damon-Runyon Postdoctoral Fellowship (to M.T.), NIH awards K08-DK62884 (to P.J.H.) and K08-AG21613 (to M.T.), an EMBO Long-Term Fellowship (to P.-O.V.), and NIH grants 5RO1HG01715-02 (NHGRI and NIGMS) and 7R33CA81658-02 (NCI) (to M.V.). ",
year = "2004",
month = feb,
day = "27",
doi = "10.1016/S1097-2765(04)00033-4",
language = "English (US)",
volume = "13",
pages = "469--482",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "4",
}