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XB-ART-47232
J Biol Chem. March 25, 2005; 280 (12): 11740-8.

Wnt-dependent regulation of the E-cadherin repressor snail.

Yook JI , Li XY , Ota I , Fearon ER , Weiss SJ .


Abstract
Down-regulation of E-cadherin marks the initiation of the epithelial-mesenchymal transition, a process exploited by invasive cancer cells. The zinc finger transcription factor, Snail, functions as a potent repressor of E-cadherin expression that can, acting alone or in concert with the Wnt/beta-catenin/T cell factor axis, induce an epithelial-mesenchymal transition. Although mechanisms that coordinate signaling events initiated by Snail and Wnt remain undefined, we demonstrate that Snail displays beta-catenin-like canonical motifs that support its GSK3beta-dependent phosphorylation, beta-TrCP-directed ubiquitination, and proteasomal degradation. Accordingly, Wnt signaling inhibits Snail phosphorylation and consequently increases Snail protein levels and activity while driving an in vivo epithelial-mesenchymal transition that is suppressed following Snail knockdown. These findings define a potential mechanism whereby Wnt signaling stabilizes Snail and beta-catenin proteins in tandem fashion so as to cooperatively engage transcriptional programs that control an epithelial-mesenchymal transition.

PubMed ID: 15647282
Article link: J Biol Chem.
Grant support: R01 CA071699 NCI NIH HHS , R01 CA071699 NCI NIH HHS , R01 CA071699 NCI NIH HHS , R01 CA071699 NCI NIH HHS , R01 CA071699 NCI NIH HHS , R01 CA071699 NCI NIH HHS , R01 CA085463 NCI NIH HHS , R01 CA085463 NCI NIH HHS , R01 CA085463 NCI NIH HHS , R01 CA085463 NCI NIH HHS , R01 CA085463 NCI NIH HHS , R01 CA085463 NCI NIH HHS , R01 CA088308 NCI NIH HHS , R01 CA088308 NCI NIH HHS , R01 CA088308 NCI NIH HHS , R01 CA088308 NCI NIH HHS , R01 CA088308 NCI NIH HHS , R01 CA088308 NCI NIH HHS

Genes referenced: btrc cdh1 gsk3b snai1
Antibodies referenced: Btrc Ab1
Morpholinos referenced:

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