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Cytokine Growth Factor Rev. 2000 Mar-Jun;11(1-2):15-22.

TGF-beta signaling by Smad proteins.

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Department of Biochemistry, The Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), 1-37-1 Kami-ikebukuro, Toshima-ku, Tokyo, Japan.


Smads are signal transducers for the members of the transforming growth factor-beta (TGF-beta) superfamily. Bone morphogenetic proteins (BMPs) and their receptors induce differentiation of C2C12 cells into osteoblast-like cells. Using an adenoviral expression vector system, we showed that receptor-regulated Smads (R-Smads) activated by BMPs can induce the differentiation of C2C12 cells. Inhibitory Smads (I-Smads) interfere with the osteoblast differentiation of C2C12 cells by preventing the nuclear translocation of R-Smads. After translocation into the nucleus, Smad oligomers regulate the transcription of target genes through binding to DNA directly, interaction with other DNA binding proteins, and recruitment of transcriptional co-activators or co-repressors. Through interaction with different transcription factors and transcriptional co-activators or co-repressors, Smads may exhibit specific effects in various cell types.

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