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The phosphorylated-r-SMAD1/5/8:Co-SMAD complex rapidly translocates to the nucleus where it binds directly to DNA and interacts with a plethora of transcription co-factors. Regulation of target gene expression can be either positive or negative. A classic example of a target gene of the pathway are the genes encoding for i-SMADs. Thus, BMP2/SMAD signalling induces the expression of the negative regulators of the pathway (a negative feedback loop).
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