Coordinate regulation of cell growth and differentiation by TGF-β superfamily and Runx proteins
Coordinate regulation of cell growth and differentiation by TGF-β superfamily and Runx proteins
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DOI：
10.1038/sj.onc.1207131
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发表时间：
2004-05-24
期刊：
影响因子：
8
通讯作者：
Imamura, T
中科院分区：
文献类型：
--
作者：
Miyazono, K;Maeda, S;Imamura, T
Runx蛋白调节各种生物过程，包括造血细胞、淋巴细胞、成骨细胞和胃上皮细胞的生长和分化。Runx蛋白的一些生物学活性使人想起转化生长因子（TGF）-β超家族细胞因子的那些。与此概念一致，受体调节的Smads（R-Smads），TGF-β超家族细胞因子的信号介导剂，和Runx蛋白已被证明彼此物理相互作用。由TGF-β和Runx蛋白激活的R-Smads协同诱导B淋巴细胞中伊加的合成，并且由骨形态发生蛋白和Runx 2激活的R-Smads诱导成骨细胞分化。此外，R-Smad-Runx信号传导途径受E3泛素连接酶Smurf 1以及干扰素信号转导子STAT 1的调节。由于Runxl和Runx 3参与包括急性白血病和胃癌在内的一些癌症的发展，因此详细检查TGF-β特异性R-Smads和Runx蛋白是否协同调节造血细胞和胃上皮细胞的生长和分化将是令人感兴趣的。
Runx proteins regulate various biological processes, including growth and differentiation of hematopoietic cells, lymphocytes, osteoblasts, and gastric epithelial cells. Some of the biological activities of Runx proteins are reminiscent of those of transforming growth factor (TGF)-beta superfamily cytokines. Consistent with this notion, receptor-regulated Smads (R-Smads), signal mediators of the TGF-beta superfamily cytokines, and Runx proteins have been shown to physically interact with each other. R-Smads activated by TGF-beta and Runx proteins cooperatively induce synthesis of IgA in B lymphocytes, and those activated by bone morphogenetic proteins and Runx2 induce osteoblastic differentiation. Moreover, the R-Smad-Runx signaling pathways are regulated by an E3 ubiquitin ligase Smurf1, as well as a signal transducer of interferons, STAT1. Since Runxl and Runx3 are involved in the development of some cancers including acute leukemia and gastric cancer, it will be of interest to examine in detail whether TGF-beta-specific R-Smads and Runx proteins coordinately regulate growth and differentiation of hematopoietic cells and gastric epithelial cells.