Regulation of Smad activity in the nucleus. (a) SARS-CoV N protein interacts with Smad3 and enhances the Smad3-p300 interaction, potentiating the Smad3-mediated transcription of fibrotic genes. SARS-CoV N protein can also interfere with the complex formation between Smad3 and Smad4, thereby inhibiting Smad4-mediated expression of apoptotic genes. (b) Smad7 directly binds to DNA and represses TGF-β signaling by interfering with the functional R-Smad/Smad4-DNA complex on target gene promoters. (c) YY1 can cooperate with Smad7 to inhibit TGF-β signaling in the nucleus via recruiting HDAC1.
