TGF-beta signaling by Smad proteins.
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.
Miyazono
K
K
Department of Biochemistry, The Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), 1-37-1 Kami-ikebukuro, Toshima-ku, Tokyo, Japan. miyazono-ind@umin.ac.jp
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D017978:Receptors, Growth Factor; D015398:Signal Transduction; D051785:Smad Proteins; D051898:Smad1 Protein; D051902:Smad5 Protein; D051905:Smad6 Protein; D051906:Smad7 Protein; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; C497399:SMAD1 protein, human; C497797:SMAD5 protein, human; C497802:SMAD6 protein, human; C497806:SMAD7 protein, human; D051785:Smad Proteins; D051898:Smad1 Protein; D051902:Smad5 Protein; D051905:Smad6 Protein; D051906:Smad7 Protein; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C060614:SKI protein, human; D052004:Bone Morphogenetic Protein Receptors