Smad6 as a transcriptional corepressor.
Smad6 and Smad7, a subgroup of Smad proteins, antagonize the signals elicited by transforming growth factor-beta. These two Smads, induced by transforming growth factor-beta or bone morphogenetic protein (BMP) stimulation, form stable associations with their activated type I receptors, blocking phosphorylation of receptor-regulated Smads in the cytoplasm. Here we show that Smad6 interacts with homeobox (Hox) c-8 as a transcriptional corepressor, inhibiting BMP signaling in the nucleus. The interaction between Smad6 and Hoxc-8 was identified by a yeast two-hybrid approach and further demonstrated by co-immunoprecipitation assays in cells. Gel shift assays show that Smad6, but not Smad7, interacts with both Hoxc-8 and Hoxa-9 as a heterodimer when binding to DNA. More importantly, the Smad6-Hoxc-8 complex inhibits interaction of Smad1 with Hoxc-8- and Smad1-induced transcription activity. These data indicate that Smad6 interacts with Hox transcription factors as part of the negative feedback circuit in the BMP signaling pathway.
Bai
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S
Department of Pathology, University of Alabama School of Medicine, Birmingham, Alabama 35294, USA.
Shi
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X
Yang
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Cao
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X
D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002467:Cell Nucleus; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005246:Feedback; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000378:metabolism*; D053495:Osteopontin; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000235:genetics; D015398:Signal Transduction; D051785:Smad Proteins; D051905:Smad6 Protein; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C080041:Hoxc6 protein, mouse; D012097:Repressor Proteins; D012795:Sialoglycoproteins; D051785:Smad Proteins; D051905:Smad6 Protein; C506896:Spp1 protein, mouse; D015534:Trans-Activators; D053495:Osteopontin