Wilms tumor suppressor WTX negatively regulates WNT/beta-catenin signaling.
Science
; 316(5827): 1043-6, 2007 May 18.
Article
em En
| MEDLINE
| ID: mdl-17510365
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.
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Proteínas Supressoras de Tumor
/
Proteínas Wnt
/
Beta Catenina
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article