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
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
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping