New regulators of Wnt/β-catenin signaling revealed by integrative molecular screening

Michael B. Major, Brian S. Roberts, Jason D. Berndt, Shane Marine, Jamie Anastas, Namjin Chung, Marc Ferrer, Xian Hua Yi, Cristi L. Stoick-Cooper, Priska D. Von Haller, Lorna Kategaya, Andy Chien, Stephane Angers, Michael MacCoss, Michele A. Cleary, William T. Arthur, Randall T. Moon

Research output: Contribution to journalArticlepeer-review

127 Scopus citations

Abstract

The identification and characterization of previously unidentified signal transduction molecules has expanded our understanding of biological systems and facilitated the development of mechanism-based therapeutics. We present a highly validated small interfering RNA (siRNA) screen that functionally annotates the human genome for modulation of the Wnt/β-catenin signal transduction pathway. Merging these functional data with an extensive Wnt/β-catenin protein interaction network produces an integrated physical and functional map of the pathway. The power of this approach is illustrated by the positioning of siRNA screen hits into discrete physical complexes of proteins. Similarly, this approach allows one to filter discoveries made through protein-protein interaction screens for functional contribution to the phenotype of interest. Using this methodology, we characterized AGGF1 as a nuclear chromatin-associated protein that participates in β-catenin-mediated transcription in human colon cancer cells.

Original languageEnglish
Pages (from-to)ra12
JournalScience signaling
Volume1
Issue number45
DOIs
StatePublished - Nov 11 2008

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