Smad7 stabilizes beta-catenin binding to E-cadherin complex and promotes cell-cell adhesion.
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.
Tang
Yi
Y
Department of Pathology, University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, AL 35294, USA.
Liu
Zhongyu
Z
Zhao
Ling
L
Clemens
Thomas L
TL
Cao
Xu
X
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D060466:Axin Protein; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D051379:Mice; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D060466:Axin Protein; D015820:Cadherins; D046912:Multiprotein Complexes; D012097:Repressor Proteins; C497806:SMAD7 protein, human; D051906:Smad7 Protein; C497807:Smad7 protein, mouse; D051153:Wnt Proteins; D051176:beta Catenin; C471641:SMURF2 protein, human; D044767:Ubiquitin-Protein Ligases; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3