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ArtikelWilms Tumor Suppressor WTX Negatively Regulates WNT/B-Catenin Signaling  
Oleh: Major, Michael B ; Camp, Nathan D. ; Berndt, Jason D ; Yi, XianHua ; Goldenberg, Seth J. ; Hubbert, Charlotte ; Biechele, Travis L ; Gingras, Anne-Claude ; Zheng, Ning ; MacCoss, Michael J ; Angers, Stephane ; Moon, Randall T.
Jenis: Article from Bulletin/Magazine
Dalam koleksi: SCIENCE (keterangan: ada di Proquest) vol. 316 no. 5827 (May 2007), page 1043.
Topik: Cell Biology
Ketersediaan
  • Perpustakaan FK
    • Nomor Panggil: S01.K.2007.05
    • Non-tandon: 1 (dapat dipinjam: 0)
    • Tandon: tidak ada
    Lihat Detail Induk
Isi artikelAberrant WNT signal transduction is involved in many diseases. In colorectal cancer and melanoma, mutational disruption of proteins involved in the degradation of B-catenin, the key effector of the WNT signaling pathway, results in stabilization of B-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 B-catenin destruction complex. This assay revealed that WTX, a protein encoded by a gene mutated in Wilms tumors, forms a complex with B-catenin, AXIN1, B-TrCP2 (B-transducin repeat-containing protein 2), and APC (adenomatous polyposis coli). Functional analyses in cultured cells, Xenopus, and zebrafish demonstrate that WTX promotes B-catenin ubiquitination and degradation, which antagonize WNT/B-catenin signaling. These data provide a possible mechanistic explanation for the tumor suppressor activity of WTX.
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