title: Smad3 prevents beta-catenin degradation and facilitates beta-catenin nuclear translocation in chondrocytes.
abstract: Our previous study demonstrated that transforming growth factor (TGF)-beta activates beta-catenin signaling through Smad3 interaction with beta-catenin in chondrocytes. In the present studies, we further investigated the detailed molecular mechanism of the cross-talk between TGF-beta/Smad3 and Wnt/beta-catenin signaling pathways. We found that C-terminal Smad3 interacted with both the N-terminal region and the middle region of beta-catenin protein in a TGF-beta-dependent manner. Both Smad3 and Smad4 were required for the interaction with beta-catenin and protected beta-catenin from an ubiquitin-proteasome-dependent degradation. In addition, the formation of the Smad3-Smad4-beta-catenin protein complex also mediated beta-catenin nuclear translocation. This Smad3-mediated regulatory mechanism of beta-catenin protein stability enhanced the activity of beta-catenin to activate downstream target genes during chondrogenesis. Our findings demonstrate a novel mechanism between TGF-beta and Wnt/beta-catenin signaling pathways during chondrocyte development.
authors.affiliation: Department of Orthopaedics and Rehabilitation, Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York 14642, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Meina
authors.initials: M
authors.lastname: Wang
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Tan
authors.forename: Tian-Fang
authors.initials: TF
authors.lastname: Li
authors.forename: Ying E
authors.initials: YE
authors.lastname: Zhang
authors.forename: Di
authors.initials: D
authors.lastname: Chen
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D019902:Chondrocytes / Q000378:metabolism*; D020219:Chondrogenesis; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D051381:Rats; D015398:Signal Transduction; D051900:Smad3 Protein / Q000378:metabolism*; D051901:Smad4 Protein / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C497790:SMAD3 protein, human; C497796:SMAD4 protein, human; D051900:Smad3 Protein; D051901:Smad4 Protein; D051153:Wnt Proteins; D051176:beta Catenin