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

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

Correspondence to: S-C Bae, E-mail: scbae@med.chungbuk.ac.kr

The Runx family of transcription factors plays pivotal roles during normal development and in neoplasias. In mammals, Runx family genes are composed of Runx1 (Pebp2B/Cbfa2/Aml1), Runx2 (Pebp2A/Cbfa1/Aml3) and Runx3 (Pebp2C/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-1 (TGF-1) 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-1 and BMP-2. Our results demonstrate that following TGF- and BMP induction, both the Smad and p38 MAPK pathways converge at the Runx2 gene to control mesenchymal precursor cell differentiation.

Oncogene (2002) 21, 7156-7163. doi:10.1038/sj.onc.1205937

Runx2; junB; p38; TGF-1; BMP-2; osteoblast