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
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
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DOI：
10.1038/sj.onc.1205937
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发表时间：
2002-10-17
期刊：
影响因子：
8
通讯作者：
Bae, SC
中科院分区：
文献类型：
--
作者：
Lee, KS;Hong, SH;Bae, SC
Runx家族的转录因子在正常发育和neoptasias中起着关键作用。在哺乳动物中，Runx家族基因由Runx 1（Pehp 2alphaB/Chfa 2/Aml 1）、Runx 2（Pebp 2alphaA/Cbfa 1/Aml 3）和Runx 3（Pehp 2alphaC/Cbfa 3/Aml 2）组成。已知Runx 1和Runx 3分别参与白血病发生和胃癌发生。另一方面，Runx 2是转化生长因子-β 1（TGF-β 1）和骨形态发生蛋白-2（BMP-2）的共同靶点，在成骨细胞分化中起重要作用。Runx 2由受体激活的Smad诱导; Runx 2介导肌源性分化的阻断并诱导C2 C12多能间充质前体细胞中的成骨细胞分化。然而，Smad不直接诱导Runx 2表达;需要额外的从头蛋白质合成步骤。在这里，我们报告，Smad诱导的junB功能作为上游激活Runx 2表达。此外，不仅Smad途径，而且丝裂原活化蛋白激酶（MAPK）级联参与TGF-β 1和BMP-2诱导Runx 2。我们的研究结果表明，TGF-β和RMP诱导后，Smad和p38 MAPK途径都会聚在Runx 2基因控制间充质前体细胞分化。
The Runx family of transcription factors plays pivotal roles during normal development and in neoptasias. In mammals, Runx family genes are composed of Runx1 (Pehp2alphaB/Chfa2/Aml1), Runx2 (Pebp2alphaA/Cbfa1/Aml3) and Runx3 (Pehp2alphaC/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-beta1 (TGF-beta1) 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-beta1 and BMP-2. Our results demonstrate that following TGF-beta and RMP induction, both the Smad and p38 MAPK pathways converge at the Runx2 gene to control mesenchymal precursor cell differentiation.