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Wnt-dependent Regulation of the E-cadherin Repressor Snail

Authors
 Jong In Yook  ;  Xiao-Yan Li  ;  Ichiro Ota  ;  Eric R. Fearon  ;  Stephen J. Weiss 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.280(12) : 11740-11748, 2005 
Journal Title
 JOURNAL OF BIOLOGICAL CHEMISTRY 
ISSN
 0021-9258 
Issue Date
2005
MeSH
Amino Acid Sequence ; Animals ; Cadherins/genetics* ; Cadherins/physiology ; Chickens ; DNA-Binding Proteins/chemistry ; DNA-Binding Proteins/physiology* ; Epithelium/pathology ; Glycogen Synthase Kinase 3/physiology ; Glycogen Synthase Kinase 3 beta ; Humans ; Intercellular Signaling Peptides and Proteins/physiology* ; Mesoderm/pathology ; Molecular Sequence Data ; Neoplasm Invasiveness ; Neoplasms/pathology* ; Phosphorylation ; Repressor Proteins/physiology* ; Snail Family Transcription Factors ; Transcription Factors/chemistry ; Transcription Factors/physiology* ; Wnt Proteins ; beta-Transducin Repeat-Containing Proteins/physiology
Keywords
15647282
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.
Files in This Item:
T200500272.pdf Download
DOI
10.1074/jbc.M413878200
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
Yonsei Authors
Yook, Jong In(육종인) ORCID logo https://orcid.org/0000-0002-7318-6112
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/147519
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