PUBLICATION
Wilms tumor suppressor WTX negatively regulates WNT/beta-catenin signaling
- Authors
- Major, M.B., Camp, N.D., Berndt, J.D., Yi, X., Goldenberg, S.J., Hubbert, C., Biechele, T.L., Gingras, A.C., Zheng, N., Maccoss, M.J., Angers, S., and Moon, R.T.
- ID
- ZDB-PUB-070523-22
- Date
- 2007
- Source
- Science (New York, N.Y.) 316(5827): 1043-1046 (Journal)
- Registered Authors
- Berndt, Jason, Moon, Randall T.
- Keywords
- none
- MeSH Terms
-
- Adaptor Proteins, Signal Transducing
- Adenomatous Polyposis Coli Protein/metabolism
- Animals
- Axin Protein
- Cell Line
- Cell Line, Tumor
- Cell Nucleus/metabolism
- Cytoplasm/metabolism
- Genes, Wilms Tumor
- Humans
- Kidney Neoplasms/genetics
- Protein Binding
- Protein Interaction Mapping
- Proteomics
- RNA Interference
- Recombinant Fusion Proteins/metabolism
- Repressor Proteins/metabolism
- Signal Transduction*
- Transduction, Genetic
- Tumor Suppressor Proteins/chemistry
- Tumor Suppressor Proteins/genetics
- Tumor Suppressor Proteins/metabolism*
- Ubiquitin/metabolism
- Ubiquitin-Protein Ligases/metabolism
- Wilms Tumor/genetics
- Wnt Proteins/metabolism*
- Xenopus Proteins
- Zebrafish
- beta Catenin/metabolism*
- beta-Transducin Repeat-Containing Proteins/metabolism
- PubMed
- 17510365 Full text @ Science
Citation
Major, M.B., Camp, N.D., Berndt, J.D., Yi, X., Goldenberg, S.J., Hubbert, C., Biechele, T.L., Gingras, A.C., Zheng, N., Maccoss, M.J., Angers, S., and Moon, R.T. (2007) Wilms tumor suppressor WTX negatively regulates WNT/beta-catenin signaling. Science (New York, N.Y.). 316(5827):1043-1046.
Abstract
Aberrant WNT signal transduction is involved in many diseases. In colorectal cancer and melanoma, mutational disruption of proteins involved in the degradation of beta-catenin, the key effector of the WNT signaling pathway, results in stabilization of beta-catenin and, in turn, activation of transcription. We have used tandem-affinity protein purification and mass spectrometry to define the protein interaction network of the beta-catenin destruction complex. This assay revealed that WTX, a protein encoded by a gene mutated in Wilms tumors, forms a complex with beta-catenin, AXIN1, beta-TrCP2 (beta-transducin repeat-containing protein 2), and APC (adenomatous polyposis coli). Functional analyses in cultured cells, Xenopus, and zebrafish demonstrate that WTX promotes beta-catenin ubiquitination and degradation, which antagonize WNT/beta-catenin signaling. These data provide a possible mechanistic explanation for the tumor suppressor activity of WTX.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping