The E3 ubiquitin ligase WWP2 facilitates RUNX2 protein transactivation in a mono-ubiquitination manner during osteogenic differentiation.

The Journal of Biological Chemistry
Wei ZhuXiaoqing Gan

Abstract

Poly-ubiquitination-mediated RUNX2 degradation is an important cause of age- and inflammation-related bone loss. NEDD4 family E3 ubiquitin protein ligases are thought to be the major regulators of RUNX2 poly-ubiquitination. However, we observed a mono-ubiquitination of RUNX2 that was catalyzed by WWP2, a member of the NEDD4 family of E3 ubiquitin ligases. WWP2 has been reported to catalyze the mono-ubiquitination of Goosecoid in chondrocytes, facilitating craniofacial skeleton development. In this study, we found that osteogenic differentiation of mesenchymal stem cells promoted WWP2 expression and nuclear accumulation. Knockdown of Wwp2 in mesenchymal stem cells and osteoblasts led to significant deficiencies of osteogenesis, including decreased mineral deposition and down-regulation of osteogenic marker genes. Co-immunoprecipitation experiments showed the interaction of WWP2 with RUNX2 in vitro and in vivo Mono-ubiquitination by WWP2 leads to RUNX2 transactivation, as evidenced by the wild type of WWP2, but not its ubiquitin ligase-dead mutant, augmenting RUNX2-reponsive reporter activity. Moreover, deletion of WWP2-dependent mono-ubiquitination resulted in striking defects of RUNX2 osteoblastic activity. In addition, ectopic...Continue Reading

References

Aug 15, 1995·Proceedings of the National Academy of Sciences of the United States of America·H I Chen, M Sudol
Apr 24, 2002·Developmental Cell·Gerard Karsenty, Erwin F Wagner
Nov 16, 2002·Nature Genetics·Carolina A YoshidaToshihisa Komori
Nov 16, 2002·Nature Genetics·Mondira KunduP Paul Liu
Mar 24, 2005·Journal of Cellular Biochemistry·Toshihisa Komori
Aug 16, 2005·Science·Jeong-Ho HongMichael B Yaffe
Sep 22, 2005·Cell and Tissue Research·Guoliang GuH Kalervo Väänänen
Dec 24, 2005·The Journal of Biological Chemistry·Hiroyuki KanekiLianping Xing
Apr 15, 2006·The Journal of Biological Chemistry·Eun-Joo JeonSuk-Chul Bae
Jun 11, 2008·The Journal of Cell Biology·Xueni LiZhijie Chang
May 14, 2009·Nature Reviews. Molecular Cell Biology·Daniela Rotin, Sharad Kumar
Feb 18, 2010·Proceedings of the National Academy of Sciences of the United States of America·Syed A AliGary S Stein
Mar 5, 2010·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Lan ZhaoLianping Xing
Aug 6, 2010·Nature·Eliezer CaloJacqueline A Lees
Mar 24, 2011·Nature Communications·Yukio NakamuraHaruhiko Akiyama
Dec 23, 2011·Nature Reviews. Molecular Cell Biology·Fanxin Long
Dec 12, 2012·Journal of Cellular Biochemistry·Krishna M Sinha, Xin Zhou
Feb 21, 2013·Current Osteoporosis Reports·Monique BethelMelissa A Kacena
Apr 5, 2013·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Lei ShuLianping Xing
Mar 18, 2016·ACS Biomaterials Science & Engineering·Arun R ShrivatsJeffrey O Hollinger
Mar 24, 2016·Stem Cell Research & Therapy·Emmanuel GibonStuart B Goodman

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