Abstract
Smad6 and Smad7, a subgroup of Smad proteins, antagonize the signals elicited by transforming growth factor-β. These two Smads, induced by transforming growth factor-β 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 8267-8270 |
| Number of pages | 4 |
| Journal | Journal of Biological Chemistry |
| Volume | 275 |
| Issue number | 12 |
| DOIs | |
| State | Published - Mar 24 2000 |
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ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
Smad6 as a transcriptional corepressor. / Bai, Shuting; Shi, Xingming; Yang, Xiangli; Xu, Cao.
In: Journal of Biological Chemistry, Vol. 275, No. 12, 24.03.2000, p. 8267-8270.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Smad6 as a transcriptional corepressor
AU - Bai, Shuting
AU - Shi, Xingming
AU - Yang, Xiangli
AU - Xu, Cao
PY - 2000/3/24
Y1 - 2000/3/24
N2 - Smad6 and Smad7, a subgroup of Smad proteins, antagonize the signals elicited by transforming growth factor-β. These two Smads, induced by transforming growth factor-β 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.
AB - Smad6 and Smad7, a subgroup of Smad proteins, antagonize the signals elicited by transforming growth factor-β. These two Smads, induced by transforming growth factor-β 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0034708801&partnerID=8YFLogxK
U2 - 10.1074/jbc.275.12.8267
DO - 10.1074/jbc.275.12.8267
M3 - Article
C2 - 10722652
AN - SCOPUS:0034708801
VL - 275
SP - 8267
EP - 8270
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 12
ER -