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

doi:10.1016/j.bone.2015.02.026

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

Department of Life Science

Research output: Contribution to journal › Article › peer-review

28 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 language	English
Pages (from-to)	201-209
Number of pages	9
Journal	Bone
Volume	75
DOIs	https://doi.org/10.1016/j.bone.2015.02.026
State	Published - 1 Jun 2015

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korean government (MSIP) to KYL ( NRF-2013R1A2A2A07067609 ), YHC ( 2014R1A6A3A01059423 ) and CYY ( 2012R1A5A1048236 ).

Publisher Copyright:
© 2015 Elsevier Inc.

Keywords

Cbl
Osteoblast differentiation
Osterix
Ubiquitination

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10.1016/j.bone.2015.02.026

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title = "Cbl-b and c-Cbl negatively regulate osteoblast differentiation by enhancing ubiquitination and degradation of Osterix",

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.",

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author = "Choi, {You Hee} and Younho Han and Lee, {Sung Ho} and Jin, {Yun Hye} and Minjin Bahn and Hur, {Kyu Chung} and Yeo, {Chang Yeol} and Lee, {Kwang Youl}",

note = "Funding Information: This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korean government (MSIP) to KYL ( NRF-2013R1A2A2A07067609 ), YHC ( 2014R1A6A3A01059423 ) and CYY ( 2012R1A5A1048236 ). Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

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doi = "10.1016/j.bone.2015.02.026",

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AU - Choi, You Hee

AU - Han, Younho

AU - Lee, Sung Ho

AU - Jin, Yun Hye

AU - Bahn, Minjin

AU - Hur, Kyu Chung

AU - Yeo, Chang Yeol

AU - Lee, Kwang Youl

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PY - 2015/6/1

Y1 - 2015/6/1

N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

Keywords

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