title: Pin1-mediated Modification Prolongs the Nuclear Retention of β-Catenin in Wnt3a-induced Osteoblast Differentiation.
abstract: The canonical Wnt signaling pathway, in which β-catenin nuclear localization is a crucial step, plays an important role in osteoblast differentiation. Pin1, a prolyl isomerase, is also known as a key enzyme in osteogenesis. However, the role of Pin1 in canonical Wnt signal-induced osteoblast differentiation is poorly understood. We found that Pin1 deficiency caused osteopenia and reduction of β-catenin in bone lining cells. Similarly, Pin1 knockdown or treatment with Pin1 inhibitors strongly decreased the nuclear β-catenin level, TOP flash activity, and expression of bone marker genes induced by canonical Wnt activation and vice versa in Pin1 overexpression. Pin1 interacts directly with and isomerizes β-catenin in the nucleus. The isomerized β-catenin could not bind to nuclear adenomatous polyposis coli, which drives β-catenin out of the nucleus for proteasomal degradation, which consequently increases the retention of β-catenin in the nucleus and might explain the decrease of β-catenin ubiquitination. These results indicate that Pin1 could be a critical target to modulate β-catenin-mediated osteogenesis.
authors.affiliation: From the Departments of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, and.
authors.forename: Hye-Rim
authors.initials: HR
authors.lastname: Shin
authors.affiliation: From the Departments of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, and.
authors.forename: Rabia
authors.initials: R
authors.lastname: Islam
authors.affiliation: From the Departments of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, and.
authors.forename: Won-Joon
authors.initials: WJ
authors.lastname: Yoon
authors.affiliation: From the Departments of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, and.
authors.forename: Taegyung
authors.initials: T
authors.lastname: Lee
authors.affiliation: From the Departments of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, and; Periodontology, School of Dentistry, Seoul National University, Seoul, 110-749, Korea.
authors.forename: Young-Dan
authors.initials: YD
authors.lastname: Cho
authors.affiliation: From the Departments of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, and.
authors.forename: Han-Sol
authors.initials: HS
authors.lastname: Bae
authors.affiliation: From the Departments of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, and.
authors.forename: Bong-Su
authors.initials: BS
authors.lastname: Kim
authors.affiliation: From the Departments of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, and.
authors.forename: Kyung-Mi
authors.initials: KM
authors.lastname: Woo
authors.affiliation: From the Departments of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, and.
authors.forename: Jeong-Hwa
authors.initials: JH
authors.lastname: Baek
authors.affiliation: From the Departments of Molecular Genetics, School of Dentistry and Dental Research Institute, BK21 Program, and. Electronic address: hmryoo@snu.ac.kr.
authors.forename: Hyun-Mo
authors.initials: HM
authors.lastname: Ryoo
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D060509:Wnt3A Protein / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D060509:Wnt3A Protein; D051176:beta Catenin; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse
keywords: Wnt signaling; adenomatous polyposis coli (APC); cell differentiation; nuclear translocation; osteoblast; osteogenesis; peptidyl prolyl cis-trans isomerization; peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1); β-catenin