Yin Yang 1 (YY1) synergizes with Smad7 to inhibit TGF-β signaling in the nucleus.

As a prototype of the TGF-β superfamily cytokines, TGF-β is well known for its diverse roles in embryogenesis and adult tissue homeostasis. TGF-β evokes cellular responses by signaling mainly through cell membrane receptors and transcription factor R-Smads and Co-Smad (Smad4), while an inhibitory Smad, Smad7, acts as a critical negative regulator of TGF-β signaling. Smad7 antagonizes TGF-β signaling by regulating the stability or activity of the receptors or blocking the DNA binding of the functional R-Smad-Smad4 complex in the nucleus.