PUBLICATION
The KLHL12-Cullin-3 ubiquitin ligase negatively regulates the Wnt-beta-catenin pathway by targeting Dishevelled for degradation
- Authors
- Angers, S., Thorpe, C.J., Biechele, T.L., Goldenberg, S.J., Zheng, N., Maccoss, M.J., and Moon, R.T.
- ID
- ZDB-PUB-060323-28
- Date
- 2006
- Source
- Nature cell biology 8(4): 348-357 (Journal)
- Registered Authors
- Moon, Randall T., Thorpe, Chris
- Keywords
- none
- MeSH Terms
-
- Adaptor Proteins, Signal Transducing/metabolism*
- Animals
- Blotting, Western
- Carrier Proteins/physiology*
- Cell Cycle Proteins/physiology*
- Cell Line
- Chromatography, Affinity
- Cullin Proteins/physiology*
- Embryo, Nonmammalian/metabolism
- Fluorescent Antibody Technique, Indirect
- Humans
- Kidney/cytology
- Microscopy, Fluorescence
- Phosphoproteins/metabolism*
- Signal Transduction*
- Ubiquitin
- Ubiquitin-Protein Ligases/physiology*
- Wnt Proteins/metabolism*
- Xenopus Proteins/physiology*
- Xenopus laevis/embryology
- Zebrafish/embryology
- Zebrafish Proteins/physiology*
- beta Catenin/metabolism*
- PubMed
- 16547521 Full text @ Nat. Cell Biol.
Citation
Angers, S., Thorpe, C.J., Biechele, T.L., Goldenberg, S.J., Zheng, N., Maccoss, M.J., and Moon, R.T. (2006) The KLHL12-Cullin-3 ubiquitin ligase negatively regulates the Wnt-beta-catenin pathway by targeting Dishevelled for degradation. Nature cell biology. 8(4):348-357.
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 a 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-ss-catenin pathway in cultured cells, as well as in Xenopus and zebrafish embryos. Considered with evidence that the distinct Cullin-1 based SCF(beta-TrCP)complex regulates beta-catenin stability, our data on the stability of Dishevelled demonstrates that two distinct ubiquitin ligase complexes regulate the Wnt-ss-catenin pathway.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping