Investigating Wnt signaling: a chemogenomic safari.
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.
McMillan
Michael
M
Institute for Chemical Genomics, Seattle, WA 98122, USA.
Kahn
Michael
M
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
D019086:Bridged Bicyclo Compounds, Heterocyclic; C492448:ICG 001; D011744:Pyrimidinones; D051820:TCF Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin