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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Ryoo, Hyun-mo Bae, Suk-chul Islam, Rabia Kim, Woo-jin Woo, Kyung-mi Cho, Young-dan Yoon, Won-joon Baek, Jeong-hwa Bae, Han-sol |
| Description | Author Affiliation: Yoon WJ ( From the Department of Molecular Genetics, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749 and.) |
| Abstract | Fibroblast growth factor 2 (FGF2) signaling plays a pivotal role in bone growth/differentiation through the activation of osteogenic master transcription factor Runx2, which is mediated by the ERK/MAPK-dependent phosphorylation and the p300-dependent acetylation of Runx2. In this study, we found that Pin1-dependent isomerization of Runx2 is the critical step for FGF2-induced Runx2 transactivation function. We identified four serine or threonine residues in the C-terminal domain of Runx2 that are responsible for Pin1 binding and structural modification. Confocal imaging studies indicated that FGF2 treatment strongly stimulated the focal accumulation of Pin1 in the subnuclear area, which recruited Runx2. In addition, active forms of RNA polymerase-II also colocalized in the same subnuclear compartment. Dipentamethylene thiuram monosulfide, a Pin1 inhibitor, strongly attenuated their focal accumulation as well as Runx2 transactivation activity. The Pin1-mediated structural modification of Runx2 is an indispensable step connecting phosphorylation and acetylation and, consequently, transcriptional activation of Runx2 by FGF signaling. Thus, the modulation of Pin1 activity may be a target for the regulation of bone formation. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 13 |
| Volume Number | 289 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2014-03-28 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cell Differentiation Drug Effects Cell Nucleus Metabolism Core Binding Factor Alpha 1 Subunit Chemistry Fibroblast Growth Factor 2 Pharmacology Osteoblasts Cytology Peptidylprolyl Isomerase Acetylation Animals Binding Sites Genetics HEK293 Cells Isomerism MAP Kinase Signaling System Mice Phosphorylation Protein Conformation Protein Stability Protein Transport Transcription, Genetic Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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