Cbl-b enhances Runx2 protein stability and augments osteocalcin promoter activity in osteoblastic cell lines.
J Cell Physiol
; 224(3): 743-7, 2010 Sep.
Article
en En
| MEDLINE
| ID: mdl-20578243
ABSTRACT
Cbl-b is a member of Cbl family of E3 ubiquitin (Ub) ligase. Besides the important role in ubiquitination process, other members of Cbl family have been suggested to show non-ubiquitination-related function in regulation of osteoblastic differentiation. However, the role of Cbl-b in regulation of osteoblastic function has not been known yet. To elucidate the role of Cbl-b in regulation of osteoblastic function, we examined its effects on Runx2, a master gene of osteoblastic differentiation. We co-expressed Cbl-b and Runx2 in osteoblastic cell lines and tested their effects on osteocalcin promoter activity together with the expression of Runx2 and its downstream genes. Luciferase assay demonstrated that Cbl-b synergistically enhances osteocalcin promoter activity in conjunction with the effect on Runx2. Co-transfection of Cbl-b and Runx2 further upregulated Runx2 protein levels without any alteration in Runx2 mRNA expression. The upregulation of Runx2 protein by Cbl-b was inhibited by the treatment with lactacystin, a specific inhibitor of the 26S proteasome. These results indicated that Cbl-b would control Runx2 protein levels at the post-translational event. Moreover, the upregulation of downstream genes of Runx2 such as osteocalcin and alkaline phosphatase mRNA was also observed. These data propose the involvement of Cbl-b in the regulation of osteoblast-related genes expression.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Osteoblastos
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Osteocalcina
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Regiones Promotoras Genéticas
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Proteínas Adaptadoras Transductoras de Señales
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Proteínas Proto-Oncogénicas c-cbl
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Subunidad alfa 1 del Factor de Unión al Sitio Principal
Límite:
Animals
Idioma:
En
Revista:
J Cell Physiol
Año:
2010
Tipo del documento:
Article
País de afiliación:
Tailandia