Article abstract
Nature Cell Biology 8, 348 - 357 (2006)
Published online: 19 March 2006 | doi:10.1038/ncb1381
The KLHL12–Cullin-3 ubiquitin ligase negatively regulates the Wnt–
-catenin pathway by targeting Dishevelled for degradation
Stephane Angers1,2, Chris J. Thorpe1,2, Travis L. Biechele1,2, Seth J. Goldenberg2, Ning Zheng2, Michael J. MacCoss3 & Randall T. Moon1,2
Abstract
Dishevelled is a conserved protein that interprets signals received by Frizzled receptors. Using a tandem-affinity purification strategy and mass spectrometry we have identified proteins associated with Dishevelled, including a Cullin-3 ubiquitin ligase complex containing the Broad Complex, Tramtrack and Bric à Brac (BTB) protein Kelch-like 12 (KLHL12). This E3 ubiquitin ligase complex is recruited to Dishevelled in a Wnt-dependent manner that promotes its poly-ubiquitination and degradation. Functional analyses demonstrate that regulation of Dishevelled by this ubiquitin ligase antagonizes the Wnt–
-catenin pathway in cultured cells, as well as in Xenopus and zebrafish embryos. Considered with evidence that the distinct Cullin-1 based SCF
-TrCPcomplex regulates 
-catenin stability, our data on the stability of Dishevelled demonstrates that two distinct ubiquitin ligase complexes regulate the Wnt–-catenin pathway.
- Howard Hughes Medical Institute, University of Washington School of Medicine, Box 357370, Seattle, WA 98195, USA.
- Department of Pharmacology, Center for Developmental Biology, University of Washington School of Medicine, Box 357370, Seattle, WA 98195, USA.
- Department of Genome Sciences, University of Washington School of Medicine, Box 357370, Seattle, WA 98195, USA.
Correspondence to: Randall T. Moon1,2 e-mail: rtmoon@u.washington.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
A role for Wnts in morpho-genesis and tissue polarityNature Cell Biology News and Views (01 Jul 2000)
Ephrins make eyes with planar cell polarityNature Cell Biology News and Views (01 Jan 2006)
See all 8 matches for News And ViewsRESEARCH
XRab40 and XCullin5 form a ubiquitin ligase complex essential for the noncanonical Wnt pathwayThe EMBO Journal Article (08 Aug 2007)
Rap2 is required for Wnt/β-catenin signaling pathway in Xenopus early developmentThe EMBO Journal Article (09 Mar 2005)
See all 55 matches for Research
