RGD Reference Report - Smad3 prevents beta-catenin degradation and facilitates beta-catenin nuclear translocation in chondrocytes. - Rat Genome Database

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Smad3 prevents beta-catenin degradation and facilitates beta-catenin nuclear translocation in chondrocytes.

Authors: Zhang, M  Wang, M  Tan, X  Li, TF  Zhang, YE  Chen, D 
Citation: Zhang M, etal., J Biol Chem. 2010 Mar 19;285(12):8703-10. doi: 10.1074/jbc.M109.093526. Epub 2010 Jan 22.
RGD ID: 11079190
Pubmed: PMID:20097766   (View Abstract at PubMed)
PMCID: PMC2838293   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M109.093526   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Smad3Ratnegative regulation of protein catabolic process involved_inIMP PMID:20097766BHF-UCL 
Smad4Ratnegative regulation of protein catabolic process involved_inIMP PMID:20097766BHF-UCL 
Smad3Ratpositive regulation of canonical Wnt signaling pathway involved_inIMP PMID:20097766CACAO 
Smad3Ratprotein stabilization involved_inIMP PMID:20097766BHF-UCL 

Cellular Component

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ctnnb1Ratnucleus part_ofIDA PMID:20097766CACAO 
Smad3Ratnucleus part_ofIDA PMID:20097766CACAO 

Molecular Function

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Smad3Ratbeta-catenin binding enablesIDA PMID:20097766BHF-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Ctnnb1  (catenin beta 1)
Smad3  (SMAD family member 3)
Smad4  (SMAD family member 4)

Additional Information