Cbl-b and c-Cbl negatively regulate osteoblast differentiation by enhancing ubiquitination and degradation of Osterix.
E3 ubiquitin ligase Cbl-b and c-Cbl play important roles in bone formation and maintenance. Cbl-b and c-Cbl regulate the activity of various receptor tyrosine kinases and intracellular protein tyrosine kinases mainly by regulating the degradation of target proteins. However, the precise mechanisms of how Cbl-b and c-Cbl regulate osteoblast differentiation ... are not well known. In this study, we investigated potential targets of Cbl-b and c-Cbl. We found that Cbl-b and c-Cbl inhibit BMP2-induced osteoblast differentiation in mesenchymal cells. Among various osteogenic transcription factors, we identified that Cbl-b and c-Cbl suppress the protein stability and transcriptional activity of Osterix. Our results suggest that Cbl-b and c-Cbl inhibit the function of Osterix by enhancing the ubiquitin-proteasome-mediated degradation of Osterix. Taken together, we propose novel regulatory roles of Cbl-b and c-Cbl during osteoblast differentiation in which Cbl-b and c-Cbl regulate the degradation of Osterix through the ubiquitin-proteasome pathway.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Cell Differentiation, Cell Line, Humans, Immunoblotting, Immunoprecipitation, Mice, Osteoblasts, Osteogenesis, Proto-Oncogene Proteins c-cbl, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factors, Transfection, Ubiquitination
Adaptor Proteins, Signal Transducing, Animals, Cell Differentiation, Cell Line, Humans, Immunoblotting, Immunoprecipitation, Mice, Osteoblasts, Osteogenesis, Proto-Oncogene Proteins c-cbl, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factors, Transfection, Ubiquitination
Bone
Date: Jun. 01, 2015
PubMed ID: 25744063
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