Abstract
Beta-catenin functions both as an adherens junction adhesion protein and as an essential mediator of the canonical Wnt signaling pathway. Wnts stabilize beta-catenin and promote its accumulation in the nucleus, where it regulates transcription of the target genes. Here we show that Smad7 promotes cell-cell adhesion by stabilizing beta-catenin and consequently increases the beta-catenin-E-cadherin complex level at the plasma membrane. A Smad7-Axin interaction disassociates GSK-3beta and beta-catenin from Axin, as well as inhibits the recruitment of Smurf2, an E3 ligase, to beta-catenin, thus protecting beta-catenin from phosphorylation and degradation. Smad7 increases the stabilized beta-catenin to form a complex with E-cadherin and stabilizes the E-cadherin-beta-catenin complex. Thereby, rather than being translocated to the nucleus for regulating the target gene transcription, Smad7-stabilized-beta-catenin is shunted to the E-cadherin complex to modulate cell-cell adhesion.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Active Transport, Cell Nucleus / physiology
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Animals
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Axin Protein
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Cadherins / genetics
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Cadherins / metabolism*
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Cell Adhesion / physiology
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Cell Line
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Cell Membrane / genetics
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Cell Membrane / metabolism*
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Cell Nucleus / genetics
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Cell Nucleus / metabolism
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Glycogen Synthase Kinase 3 / genetics
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Glycogen Synthase Kinase 3 / metabolism
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Glycogen Synthase Kinase 3 beta
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Humans
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Mice
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Multiprotein Complexes / genetics
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Multiprotein Complexes / metabolism*
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Phosphorylation
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Protein Binding / physiology
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Smad7 Protein / genetics
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Smad7 Protein / metabolism*
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Ubiquitin-Protein Ligases / genetics
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Ubiquitin-Protein Ligases / metabolism
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Wnt Proteins
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beta Catenin / genetics
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beta Catenin / metabolism*
Substances
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Axin Protein
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Cadherins
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Multiprotein Complexes
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Repressor Proteins
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SMAD7 protein, human
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Smad7 Protein
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Smad7 protein, mouse
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Wnt Proteins
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beta Catenin
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SMURF2 protein, human
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Ubiquitin-Protein Ligases
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GSK3B protein, human
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Glycogen Synthase Kinase 3 beta
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Gsk3b protein, mouse
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Glycogen Synthase Kinase 3