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

Bone
You Hee ChoiKwang Youl Lee

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.

References

Oct 6, 1999·Current Biology : CB·Y Hakak, G S Martin
Apr 25, 2000·Gene·A J Bendall, C Abate-Shen
Jul 13, 2001·The Journal of Biological Chemistry·M YokouchiR Baron
Oct 19, 2001·Oncogene·A Y TsygankovG Swaminathan
Mar 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Navin RaoHamid Band
Jul 11, 2002·Oral Diseases·T Katagiri, N Takahashi
Sep 10, 2003·Biochemical and Biophysical Research Communications·Mi-Hye LeeHyun-Mo Ryoo
Jul 16, 2005·Growth Factors·Christine B F Thien, Wallace Y Langdon
Oct 11, 2005·The Biochemical Journal·Christine B F Thien, Wallace Y Langdon
Feb 10, 2006·Biochemical and Biophysical Research Communications·Qisheng TuJake Chen
Jun 1, 2006·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Naoto SuzueNatsuo Yasui
Jun 24, 2006·Journal of Cellular Biochemistry·Toshihisa Komori
Oct 25, 2007·PloS One·Naohiro KawamuraHiroshi Kawaguchi
Dec 7, 2007·The Journal of Biological Chemistry·Arnau UlsamerFrancesc Ventura
Feb 19, 2008·Developmental Biology·Haitao LiAlexander C Lichtler
May 7, 2008·Proceedings of the National Academy of Sciences of the United States of America·Chi ZhangBenoit de Crombrugghe
May 14, 2008·Current Stem Cell Research & Therapy·Terhi J Heino, Teuvo A Hentunen
Aug 16, 2008·The Journal of Biological Chemistry·Takuma MatsubaraToshiyuki Yoneda
Mar 5, 2009·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Arata NakajimaRoland Baron
Dec 29, 2009·The Journal of Biological Chemistry·Jung Ha KimNacksung Kim
Jun 26, 2010·Journal of Cellular Physiology·R Ampornaramveth SalingcarnboriboonM Noda
Sep 29, 2011·Calcified Tissue International·Tracy BrennanArchana Sanjay
May 25, 2012·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Nicolas SévèrePierre J Marie
Jan 19, 2013·Cell Death & Disease·N SévèreP J Marie

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Citations

Aug 19, 2015·Frontiers in Cellular Neuroscience·Cedric Boeckx, Antonio Benítez-Burraco
Dec 19, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Han Yan, Barbara F Hales
Sep 16, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Seira HoshikawaHiroyuki Inuzuka
Jan 2, 2021·Frontiers in Cell and Developmental Biology·Qian LiuGuangwei Wang
Oct 30, 2020·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Ke ChenZhaohui Mo
Dec 2, 2021·Toxicological Sciences : an Official Journal of the Society of Toxicology·Lama IskandaraniBarbara F Hales

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