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Pin1, the master orchestrator of bone cell differentiation

Version 2 2024-06-13, 10:32
Version 1 2017-05-16, 14:49
journal contribution
posted on 2024-06-13, 10:32 authored by R Islam, W-J Yoon, H-M Ryoo
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.

History

Journal

Journal of Cellular Physiology

Volume

232

Pagination

2339-2347

Location

United States

ISSN

0021-9541

Language

eng

Publication classification

C Journal article, C1.1 Refereed article in a scholarly journal

Copyright notice

2016 Wiley Periodicals

Issue

9

Publisher

John Wiley & Sons