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Smad6 as a transcriptional corepressor 总被引:11,自引:0,他引:11
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Stopa M Anhuf D Terstegen L Gatsios P Gressner AM Dooley S 《The Journal of biological chemistry》2000,275(38):29308-29317
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Regulation of Smad7 promoter by direct association with Smad3 and Smad4 总被引:26,自引:0,他引:26
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Repression of endogenous Smad7 by Ski 总被引:3,自引:0,他引:3
The Ski protein has been proposed to serve as a corepressor for Smad4 to maintain a transforming growth factor-beta (TGF-beta)-responsive promoter at a repressed, basal level. However, there have been no reports so far that it indeed acts on a natural promoter. We have previously cloned the human Smad7 promoter and shown that it contains the 8-base pair palindromic Smad-binding element (SBE) necessary for TGF-beta induction. In this report, we have characterized the negative regulation of Smad7 promoter basal activity by Ski. We show that Ski inhibits the Smad7 promoter basal activity in a SBE-dependent manner. Mutation of the SBE abrogates the inhibitory effect of Ski on the Smad7 promoter. Moreover, mutation of the SBE increases the Smad7 promoter basal activity. Using the chromatin immunoprecipitation assay, we further show that Ski together with Smad4 binds to the endogenous Smad7 promoter. Finally, we show that RNAi knockdown of Ski increases Smad7 reporter gene activity in transient transfection assays as well as elevating the endogenous level of Smad7 mRNA. Taken together, our results provide the first evidence that Ski is indeed a corepressor for Smad4, which can inhibit a natural TGF-beta responsive gene at the basal state. 相似文献
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K Thirunavukkarasu R R Miles D L Halladay X Yang R J Galvin S Chandrasekhar T J Martin J E Onyia 《The Journal of biological chemistry》2001,276(39):36241-36250
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A Smad transcriptional corepressor 总被引:46,自引:0,他引:46
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