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
-
- Ubiquitin-Protein Ligases/metabolism
- Cell Line
- Proteomics
- Genes, Wilms Tumor
- beta-Transducin Repeat-Containing Proteins/metabolism
- Transduction, Genetic
- Protein Interaction Mapping
- Zebrafish
- Adaptor Proteins, Signal Transducing
- beta Catenin/metabolism*
- Cell Line, Tumor
- Wilms Tumor/genetics
- Repressor Proteins/metabolism
- RNA Interference
- Signal Transduction*
- Cell Nucleus/metabolism
- Animals
- Kidney Neoplasms/genetics
- Xenopus Proteins
- Wnt Proteins/metabolism*
- Recombinant Fusion Proteins/metabolism
- Adenomatous Polyposis Coli Protein/metabolism
- Protein Binding
- Axin Protein
- Humans
- Tumor Suppressor Proteins/chemistry
- Tumor Suppressor Proteins/genetics
- Tumor Suppressor Proteins/metabolism*
- Cytoplasm/metabolism
- Ubiquitin/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