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
  • Protein Binding
  • Genes, Wilms Tumor
  • Axin Protein
  • beta Catenin/metabolism*
  • beta-Transducin Repeat-Containing Proteins/metabolism
  • Animals
  • Xenopus Proteins
  • Adaptor Proteins, Signal Transducing
  • Cell Nucleus/metabolism
  • Zebrafish
  • Cytoplasm/metabolism
  • Ubiquitin/metabolism
  • RNA Interference
  • Humans
  • Kidney Neoplasms/genetics
  • Cell Line
  • Protein Interaction Mapping
  • Tumor Suppressor Proteins/chemistry
  • Tumor Suppressor Proteins/genetics
  • Tumor Suppressor Proteins/metabolism*
  • Wilms Tumor/genetics
  • Transduction, Genetic
  • Signal Transduction*
  • Wnt Proteins/metabolism*
  • Adenomatous Polyposis Coli Protein/metabolism
  • Recombinant Fusion Proteins/metabolism
  • Cell Line, Tumor
  • Proteomics
  • Repressor Proteins/metabolism
  • Ubiquitin-Protein Ligases/metabolism
(all 30)
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
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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.