| First Author | Yoshida K | Year | 2009 |
| Journal | Exp Cell Res | Volume | 315 |
| Issue | 12 | Pages | 2105-14 |
| PubMed ID | 19230833 | Mgi Jnum | J:150390 |
| Mgi Id | MGI:3850614 | Doi | 10.1016/j.yexcr.2009.02.003 |
| Citation | Yoshida K, et al. (2009) PKR-mediated degradation of STAT1 regulates osteoblast differentiation. Exp Cell Res 315(12):2105-14 |
| abstractText | The double-stranded RNA-dependent protein kinase (PKR) plays a critical role in various biological responses including antiviral defense, cell differentiation, apoptosis, and tumorigenesis. In this study, we investigated whether PKR could affect the post-translational modifications of STAT1 protein and whether these modifications regulate osteoblast differentiation. We demonstrated that PKR was necessary for the ubiquitination of STAT1 protein. The expressions of bone-related genes such as type I collagen, integrin binding sialoprotein, osteopontin, and osterix were suppressed in osteoblasts lacking PKR activity. In contrast, the expressions of interleukin-6 and matrix metalloproteinases 8 and 13 increased in PKR-mutated osteoblasts. The expression and degradation of STAT1 protein were regulated by PKR in a SLIM-dependent pathway. Inhibition of SLIM by RNA interference resulted in the decreased activity of Runx2 in osteoblasts. Stimulation of interleukin-6 expression and suppression of alkaline phosphatase activity were regulated through by SLIM-dependent pathway. However, expressions of bone-related genes and MMPs were regulated by SLIM-independent pathway. Our present results suggest that the aberrant accumulation of STAT1 protein induced by loss of PKR regulate osteoblast differentiation through both SLIM/STAT1-dependent and -independent pathways. |
