| First Author | Shin HR | Year | 2016 |
| Journal | J Biol Chem | Volume | 291 |
| Issue | 11 | Pages | 5555-5565 |
| PubMed ID | 26740630 | Mgi Jnum | J:315562 |
| Mgi Id | MGI:6829245 | Doi | 10.1074/jbc.M115.698563 |
| Citation | Shin HR, et al. (2016) Pin1-mediated Modification Prolongs the Nuclear Retention of beta-Catenin in Wnt3a-induced Osteoblast Differentiation. J Biol Chem 291(11):5555-5565 |
| abstractText | The canonical Wnt signaling pathway, in which beta-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 beta-catenin in bone lining cells. Similarly, Pin1 knockdown or treatment with Pin1 inhibitors strongly decreased the nuclear beta-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 beta-catenin in the nucleus. The isomerized beta-catenin could not bind to nuclear adenomatous polyposis coli, which drives beta-catenin out of the nucleus for proteasomal degradation, which consequently increases the retention of beta-catenin in the nucleus and might explain the decrease of beta-catenin ubiquitination. These results indicate that Pin1 could be a critical target to modulate beta-catenin-mediated osteogenesis. |
