title: Investigating Wnt signaling: a chemogenomic safari.
abstract: Chemical genomics is a powerful method to complement more traditional genetic techniques (i.e. knockout mice, siRNA) for the dissection of complex signaling networks. Wnt signaling in mammals is a complex and crucial regulator of diverse functions. The Wnt-beta-catenin pathway initiates a signaling cascade that is crucial in both normal development and the initiation and progression of cancer. A key step in Wnt activation of target genes is the nuclear translocation of beta-catenin and the formation of a complex between beta-catenin and members of the T-cell factor (TCF) family of transcription factors. Using a forward chemical genomics strategy, we identified ICG-001, a selective inhibitor of a subset of Wnt-beta-catenin-driven gene expression. This chemogenomic tool enables us to dissect this complex signaling network and to better understand the role of Wnt signaling in both normal and pathophysiological settings.
authors.affiliation: Institute for Chemical Genomics, Seattle, WA 98122, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: McMillan
authors.forename: Michael
authors.initials: M
authors.lastname: Kahn
mesh_terms: D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry / Q000494:pharmacology; D002454:Cell Differentiation; D049109:Cell Proliferation; D015195:Drug Design; D005786:Gene Expression Regulation; D023281:Genomics; D021381:Protein Transport; D011744:Pyrimidinones / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction; D051820:TCF Transcription Factors / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; C492448:ICG 001; D011744:Pyrimidinones; D051820:TCF Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin