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PMID:16690606
| Citation |
Li, TF, Chen, D, Wu, Q, Chen, M, Sheu, TJ, Schwarz, EM, Drissi, H, Zuscik, M and O'Keefe, RJ (2006) Transforming growth factor-beta stimulates cyclin D1 expression through activation of beta-catenin signaling in chondrocytes. J. Biol. Chem. 281:21296-304 |
|---|---|
| Abstract |
Transforming growth factor-beta (TGF-beta) plays an essential role in chondrocyte maturation. It stimulates chondrocyte proliferation but inhibits chondrocyte differentiation. In this study, we found that TGF-beta rapidly induced beta-catenin protein levels and signaling in murine neonatal sternal primary chondrocytes. TGF-beta-increased beta-catenin induction was reproduced by overexpression of SMAD3 and was absent in Smad3(-/-) chondrocytes treated with TGF-beta. SMAD3 inhibited beta-transducin repeat-containing protein-mediated degradation of beta-catenin and immunoprecipitated with beta-catenin following TGF-beta treatment. Both SMAD3 and beta-catenin co-localized to the nucleus after TGF-beta treatment. Although both TGF-beta and beta-catenin stimulated cyclin D(1) expression in chondrocytes, the effect of TGF-beta was inhibited with beta-catenin gene deletion or SMAD3 loss of function. These results demonstrate that TGF-beta stimulates cyclin D(1) expression at least in part through activation of beta-catenin signaling. |
| Links |
PubMed PMC2649822 Online version:10.1074/jbc.M600514200 |
| Keywords |
Adenoviridae/metabolism; Animals; Cell Proliferation; Chondrocytes/metabolism; Cyclin D1/biosynthesis; Gene Deletion; Mice; Mice, Transgenic; Signal Transduction; Smad3 Protein/genetics; Smad3 Protein/metabolism; Transducin/chemistry; Transforming Growth Factor beta/metabolism; Transforming Growth Factor beta/physiology; Transforming Growth Factor beta1; beta Catenin/metabolism |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0035411: catenin import into nucleus |
ECO:0000314: |
P |
Figure 3 |
complete | ||||
| GO:0005634: nucleus |
ECO:0000314: |
C |
Figure 3 shows accumulation of SMAD3 in the nucleus |
complete | ||||
| GO:0042177: negative regulation of protein catabolic process |
ECO:0000314: |
P |
Figure 4 |
complete | ||||
| GO:0005634: nucleus |
ECO:0000314: |
C |
Figure 3 shows localization of beta catenin in the nucleus |
complete | ||||
Notes
See also
References
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