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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 volume 21, pages 7156–7163 (2002)Cite this article

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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Authors and Affiliations

  1. Department of Biochemistry, School of Medicine, Chungbuk National University, Cheongju, 361-763, South Korea

    Kyeong-Sook Lee, Seung-Hyun Hong & Suk-Chul Bae

  2. Institute for Tumor Engineering, Chungbuk National University, Cheongju, 361-763, South Korea

    Seung-Hyun Hong & Suk-Chul Bae

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  1. Kyeong-Sook Lee
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Correspondence to Suk-Chul Bae.

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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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