Cbl-b and c-Cbl negatively regulate osteoblast differentiation by enhancing ubiquitination and degradation of Osterix

You Hee Choi, Younho Han, Sung Ho Lee, Yun Hye Jin, Minjin Bahn, Kyu Chung Hur, Chang Yeol Yeo, Kwang Youl Lee

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)201-209
Number of pages9
JournalBone
Volume75
DOIs
StatePublished - 1 Jun 2015

Keywords

  • Cbl
  • Osteoblast differentiation
  • Osterix
  • Ubiquitination

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