title: Pin1, the Master Orchestrator of Bone Cell Differentiation.
abstract: Pin1 is an enzyme that specifically recognizes the peptide bond between phosphorylated serine or threonine (pS/pT-P) and proline. This recognition causes a conformational change of its substrate, which further regulates downstream signaling. Pin1-/-mice show developmental bone defects and reduced mineralization. Pin1 targets RUNX2 (Runt-Related Transcription Factor 2), SMAD1/5, and β-catenin in the FGF, BMP, and WNT pathways, respectively. Pin1 has multiple roles in the crosstalk between different anabolic bone signaling pathways. For example, it controls different aspects of osteoblastogenesis and increases the transcriptional activity of Runx2, both directly and indirectly. Pin1 also influences osteoclastogenesis at different stages by targeting PU.1 (Purine-rich nucleic acid binding protein 1), C-FOS, and DC-STAMP. The phenotype of Pin1-/-mice has led to the recent identification of multiple roles of Pin1 in different molecular pathways in bone cells. These roles suggest that Pin1 can be utilized as an efficient drug target in congenital and acquired bone diseases. J. Cell. Physiol. 232: 2339-2347, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Molecular Genetics, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic of Korea.
authors.forename: Rabia
authors.initials: R
authors.lastname: Islam
authors.affiliation: Department of Molecular Genetics, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic of Korea.
authors.forename: Won-Joon
authors.initials: WJ
authors.lastname: Yoon
authors.affiliation: Department of Molecular Genetics, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic of Korea.
authors.forename: Hyun-Mo
authors.initials: HM
authors.lastname: Ryoo
mesh_terms: D000818:Animals; D001847:Bone Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D016723:Bone Remodeling; D001842:Bone and Bones / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006801:Humans; D018345:Mice, Knockout; D058990:Molecular Targeted Therapy; D000072340:NIMA-Interacting Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D010012:Osteogenesis; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D004791:Enzyme Inhibitors; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D051785:Smad Proteins; D051176:beta Catenin; D005346:Fibroblast Growth Factors; C000606846:PIN1 protein, human; C000606850:Pin1 protein, mouse