Abstract
The Runx family of transcription factors plays pivotal roles during normal development and in neoplasias. In mammals, Runx family genes are composed of Runx1 (Pebp2αB/Cbfa2/Aml1), Runx2 (Pebp2αA/Cbfa1/Aml3) and Runx3 (Pebp2αC/Cbfa3/Aml2). Runx1 and Runx3 are known to be involved in leukemogenesis and gastric carcinogenesis, respectively. Runx2, on the other hand, is a common target of transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2) and plays an essential role in osteoblast differentiation. Runx2 is induced by the receptor-activated Smad; Runx2 mediates the blockage of myogenic differentiation and induces osteoblast differentiation in C2C12 pluripotent mesenchymal precursor cells. However, Smad does not directly induce Runx2 expression; an additional step of de novo protein synthesis is required. Here we report that Smad-induced junB functions as an upstream activator of Runx2 expression. Furthermore, not only the Smad pathway but also the mitogen-activated protein kinase (MAPK) cascades are involved in the induction of Runx2 by TGF-β1 and BMP-2. Our results demonstrate that following TGF-β and BMP induction, both the Smad and p38 MAPK pathways converge at the Runx2 gene to control mesenchymal precursor cell differentiation.
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Acknowledgements
This work was supported by a grant to S-C Bae from the Molecular Medicine Research Group Program (M1-0106-00-0064) of the Ministry of Science and Technology of Korea. This work was also supported by Korean Research Foundation grant KRF-2001-042-D0067.
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Lee, KS., Hong, SH. & Bae, SC. Both the Smad and p38 MAPK pathways play a crucial role in Runx2 expression following induction by transforming growth factor-β and bone morphogenetic protein. Oncogene 21, 7156–7163 (2002). https://doi.org/10.1038/sj.onc.1205937
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DOI: https://doi.org/10.1038/sj.onc.1205937
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