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Bone morphogenetic protein-2 stimulates RUNX2 acetylation

Cited 240 time in Web of Science Cited 247 time in Scopus
Authors
Jeon, Eun-Joo; Lee, Kwang-Youl; Choi, Nam-Sook; Lee, Mi-Hye; Kim, Hyun-Nam; Jin, Yun-Hye; Ryoo, Hyun-Mo; Choi, Je-Yong; Yoshida, Minoru; Nishino, Norikazu; Oh, Byung-Chul; Lee, Kyeong-Sook; Lee, Yong Hee; Bae, Suk-Chul
Issue Date
2006-06
Publisher
The American Society for Biochemistry and Molecular Biology
Citation
The Journal of Biological Chemistry, 281, 16502-16511.
Abstract
Runx2/Cbfa1/Pebp2aA is a global regulator of osteogenesis and is crucial for regulating the expression of bone-specific genes. Runx2 is a major target of the bone morphogenetic protein (BMP) pathway. Genetic analysis has revealed that Runx2 is degraded through a Smurf-mediated ubiquitination pathway, and its activity is inhibited by HDAC4. Here, we demonstrate the molecular link between Smurf, HDACs and Runx2, in BMP signaling. BMP-2 signaling stimulates p300-mediated Runx2 acetylation, increasing transactivation activity and inhibiting Smurf1-mediated degradation of Runx2. HDAC4 and HDAC5 dea-cetylate Runx2, allowing the protein to undergo Smurf-mediated degradation. Inhibition of HDAC increases Runx2 acetylation, and potentiates BMP-2-stimulated osteoblast differentiation and increases bone formation. These results demonstrate that the level of Runx2 is controlled by a dynamic equilibrium of acetylation, deacetylation, and ubiquitination. These findings have important medical implications because BMPs and Runx2 are of tremendous interest with regard to the development of therapeutic agents against bone diseases.
ISSN
0021-9258
Language
English
URI
https://hdl.handle.net/10371/69656
DOI
https://doi.org/10.1074/jbc.M512494200
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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